Salmonella Cold Stress Response - Mechanisms and Occurrence in Foods

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Salmonella Cold Stress Response:

Mechanisms and Occurrence
in Foods
Steven C. Ricke*,†,‡,1, Turki M. Dawoud*,†,§,2, Sun Ae Kim†,‡,§,3,
Si Hong Park*,†,‡,4, Young Min Kwon*,†,§
*Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR, United States
†
Center for Food Safety, University of Arkansas, Fayetteville, AR, United States
‡
Department of Food Science, University of Arkansas, Fayetteville, AR, United States
§
Department of Poultry Science, University of Arkansas, Fayetteville, AR, United States
1
Corresponding author: e-mail address: sricke@uark.edu
Contents
1. Introduction 2
2. Molecular Mechanisms to Counter Cold Shock 4
2.1 General Concepts on Environmental Stress 4
2.2 Cold Stress: Physiological Responses 4
2.3 Cold Shock Response: Molecular Profiles 6
2.4 Cell Membrane Modification 7
2.5 DNA Supercoiling Modification 8
2.6 CIP Synthesis 9
3. Salmonella–Cold Shock Interaction With Other Stress Responses 18
3.1 Cross-Protection 18
3.2 Interaction With Virulence Responses 19
4. Salmonella Responses to Cold Temperatures in Food Production 21
4.1 Salmonella Growth, Survival, and Influential Factors 21
4.2 Beef Products 24
4.3 Chicken Meat Products 25
4.4 Other Food Products 26
5. Conclusions 27
Acknowledgments 28
References 28
2
Current address: Botany and Microbiology Department, Science College, King Saud University,
Riyadh 11451, Saudi Arabia
3
Current address: Department of Food Science and Engineering, Ewha Womans University, Seoul,
South Korea
4
Current address: Department of Food Science and Technology, Oregon State University, Corvallis,
OR, USA 97331
#
Advances in Applied Microbiology 2018 Elsevier Inc. 1
ISSN 0065-2164 All rights reserved.
https://doi.org/10.1016/bs.aambs.2018.03.001
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2 Steven C. Ricke et al.
Abstract
Since bacteria in foods often encounter various cold environments during food
processing, such as chilling, cold chain distribution, and cold storage, lower tempera-
tures can become a major stress environment for foodborne pathogens. Bacterial
responses in stressful environments have been considered in the past, but now the impor-
tance of stress responses at the molecular level is becoming recognized. Documenting
how bacterial changes occur at the molecular level may help to achieve the in-depth
understanding of stress responses, to predict microbial fate when they encounter cold
temperatures, and to design and develop more effective strategies to control pathogens
in food for ensuring food safety. Microorganisms differ in responding to a sudden down-
shift in temperature and this, in turn, impacts their metabolic processes and can cause
various structural modifications. In this review, the fundamental aspects of bacterial cold
stress responses focused on cell membrane modification, DNA supercoiling modification,
transcriptional and translational responses, cold-induced protein synthesis including
CspA, CsdA, NusA, DnaA, RecA, RbfA, PNPase, KsgA, SrmB, trigger factors, and initiation
factors are discussed. In this context, specific Salmonella responses to cold temperature
including growth, injury, and survival and their physiological and genetic responses to
cold environments with a focus on cross-protection, different gene expression levels,
and virulence factors will be discussed.
1. INTRODUCTION
Foodborne agents are responsible for numerous infectious diseases in
humans as a result of ingestion of contaminated foods. Contaminated food
and water with various pathogens have been the main vehicles of infection for
diarrheal diseases worldwide and their contamination can take place at mul-
tiple points during all stages of food production and subsequent processing
and retail (Cairncross et al., 2010; Crandall et al., 2013; Finstad, O’Bryan,
Marcy, Crandall, & Ricke, 2012; Howard, O’Bryan, Crandall, & Ricke,
2012; O’Ryan, Prado, & Pickering, 2005; Podewils, Mintz, Nataro, &
Parashar, 2004; Santosham et al., 2010; Schmidt & Cairncross, 2009).
Foodborne agents have been estimated to cause nearly 48 million illnesses
in the United States with 128,000 hospitalizations and over 3000 deaths,
which means that approximately 15% of the total US population will annually
experience a foodborne infection (Scallan et al., 2011). Thus their contam-
ination in food is considered a major public concern for both consumers and
related industries.
Salmonella is a leading source of foodborne outbreaks throughout the
world and is typically associated with the consumption of poultry, beef, lamb,
seafood, vegetables, fruits, and their food products (Brands et al., 2005;
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Salmonella Cold Stress Response 3
Davies et al., 2004; de Freitas Neto, Penha Filho, Barrow, & Berchieri Junior,
2010; Foley, Johnson, Ricke, Nayak, & Danzeisen, 2013; Foley et al., 2011;
Hanning, Nutt, & Ricke, 2009; Heaton & Jones, 2008; Heinitz, Ruble,
Wagner, & Tatini, 2000; Lynch, Tauxe, & Hedberg, 2009; Martinez-
Urtaza, Peiteado, Lozano-León, & Garcia-Martin, 2004; Pires, Viera,
Hald, & Cole, 2014; Rajashekara et al., 2000; Ricke, 2017). The infections
caused by Salmonella represent a considerable cost to the US economy annu-
ally (McClinden, Sargeant, Thomas, Papadopoulos, & Fazil, 2014; Scharff,
2012), and it is estimated that over 1 million people annually contract
Salmonella in the United States (Scallan et al., 2011). Despite some success
in limiting Salmonella in the past few years, it remains a fairly prevalent
foodborne pathogen.
In general, foodborne pathogenic bacteria can grow rapidly in temper-
atures ranging from 5°C (40°F) to 60°C (140°F), and this temperature zone
is referred to as the “danger zone” (United States Department of Agriculture
Food Safety and Inspection Service, 2013). Controlling temperature of food
to avoid this danger zone is a traditional measure to ensure food safety and
to extend the shelf life of food by limiting microbial growth. Foods such
as fresh produce, animal carcasses, and their corresponding products are
typically required to be chilled to lower temperatures throughout food
processing mainly during storage, transportation, and distribution (Archer,
2004; Buncic & Sofos, 2012; Galiş et al., 2013; Guillard, Mauricio-
Iglesias, & Gontard, 2010; Hanning et al., 2009; McDonald & Sun, 2000;
Russell, 2002). Some procedures are performed at cold temperatures, such
as cooling and/or freezing, to serve as preservation processes for effectively
reducing the bacterial burden of contaminated food (Dinçer & Baysal, 2004;
Loretz, Stephan, & Zweifel, 2010). Though these preservation procedures
using cold temperature are effective in limiting bacterial growth, exposure to
low temperatures can also lead to some concerns in regards to cold adapta-
tion, cross-protection, and unexpected modification of food-associated
microorganisms composed predominantly of spoilage microorganisms and
foodborne pathogens (Abee & Wouters, 1999; Alzamora, Tapia, &
Chanes, 1998; Beales, 2004; Berry & Foegeding, 1997). To better apply
control measures with cold temperature, an in-depth understanding of bac-
terial behavior and the corresponding response when they are exposed to cold
environments are essential.
There is limited mechanisms-based information on specific cold stress
responses of Salmonella, research on survival, injury, and growth of Salmo-
nella in cold temperatures. This review includes an overview of studies
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investigating general mechanisms associated with bacterial cold stress

responses, including cell membrane modification, DNA topology, tran-
scriptional and translational responses with a discussion on cold-induced
protein (CIP) synthesis. In addition, the physiological and genetic responses
of Salmonella in food products held at cold temperatures will be discussed,
and implications related to pathogenesis will be described.
2. MOLECULAR MECHANISMS TO COUNTER

COLD SHOCK
2.1 General Concepts on Environmental Stress
During the life cycle of a foodborne pathogen in food production such as Sal-
monella, it typically encounters a multitude of less than optimal if not downright
hostile environmental conditions. This includes environments that are preva-
lent during live animal production, transportation, at the processing plant,
retail, and homes of consumers. The types of harsh environments that Salmo-
nella and other pathogens can encounter during food production include a
wide range of physiologically challenging factors such as low water activity/
desiccation, high osmolarity, low pH/high acid concentrations, presence of
a variety of antimicrobials, and low nutrient availability leading to starvation,
just to name a few (Boor, 2006; Foster, 1999; Gyles, 2008; Park et al., 2008;
Ricke, 2003a, 2003b; Ricke, Kundinger, Miller, & Keeton, 2005; Rowley,
Spector, Kormanec, & Roberts, 2006; Spector, 1998). Not surprisingly, most
organisms possess several mechanism(s) that enable them to counter these
stresses whether they occur suddenly or more gradually allowing the organism
to transition to the most challenging environmental condition. Certainly,
temperature extremes outside optimal growth requirements whether thermal
or cold are a challenge to organisms such as Salmonella and have been detailed
over the past decades (Barria, Malecki, & Arraiano, 2013; Dawoud et al.,
2017; Eriksson, Hurme, & Rhen, 2002; Gualerzi, Giuliodori, & Pon,
2003; Jarvis et al., 2016; Panoff, Thammavongs, Gueguen, & Boutibonnes,
1998; Ramos et al., 2001; Russell, 1990; Singh, Sarin, & Tandon, 1997;
Thieringer, Jones, & Inouye, 1998). Such environmental conditions represent
stress to the organism and most microorganisms including Salmonella have the
capability to counter with an array of resistance and tolerance mechanisms.
2.2 Cold Stress: Physiological Responses

For organisms such as Salmonella, sudden encounters with cold temperatures
that occur with refrigeration and freezing in food processing/storage
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represent a major physiological challenge to the organism. This exposure

results in a halting of growth, adaptation for survival, followed by renewal
of growth under the reduced ambient temperatures (Gualerzi et al., 2003).
In general, bacterial cells exposed to cold or low temperature depending on
the microorganism’s optimal growth temperature, go through three stages
(Thieringer et al., 1998; Weber & Marahiel, 2003). The first stage is the tran-
sient response immediately after the exposure is known as acclimatization
postshock phase and the time duration for this response may vary with
regards to growth rate reduction and the gene expression and subsequent
synthesis of proteins for cold survival response. The cells next enter the sec-
ond stage known as a recovery phase, with bacterial cells growing more rap-
idly and gradually resuming cellular protein biosynthesis. In the last stage, the
cells become permanently adapted to cold temperature with gene expression
modification, and this occurs when the bacterial cells reach stationary
growth phase.
At lowered temperatures occurring during cold shock, transcriptional
and translational processes are essentially leading the ribosome to become
ineffective followed by inadequate protein folding along with cellular
protein biosynthesis decreases, and eventually a potentially adverse influ-
ence on growth rate (Chattopadhyay, 2006; Ermolenko & Makhatadze,
2002; Phadtare, 2004). Physiologically, adaptation to these harsh temper-
atures is manifested in several ways, and these mechanisms have been
summarized by Barria et al. (2013). As expected membrane integrity is
impacted by a sudden decrease in external temperatures and part of
the adaptation adjustment elicited by the bacterial cell is to adjust the
membrane composition by desaturating fatty acids to optimize the fluid-
ity for growth at lower temperatures (Thieringer et al., 1998). Intracel-
lularly, bacterial cells adjust their transcription and translation functions
in the presence of lower temperatures by optimizing RNA processing
in conjunction with changes in DNA supercoiling and continued trans-
cription of cold-induced genes and production of cold-inducible proteins
(Barria et al., 2013). Once cold temperature adapted, bacterial cells begin
growing again, and CIPs decrease as growth-related protein synthesis
resumes (Barria et al., 2013). Bacteria can also protect cellular functions
by accumulating low molecular weight solutes, including glycine beta-
ine, carnitine, and trehalose among others to retain the integrity of
cell proteins exposed to external stresses such as cold temperatures
which Shivaji and Prakash (2010) referred to collectively as “chemical
chaperones.”
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2.3 Cold Shock Response: Molecular Profiles

Several transcriptional analysis (gene expression) studies of the Escherichia coli
cold shock responses have been conducted leading to the detection of the
primary cold shock proteins (CSPs) and other genes that are involved in this
response coming from different categories of functional groups such as
motility-associated genes (flagellar-coding genes), and proteins of sugar
metabolism and transport. The CSPs, CspA, CspB, CspG, and CspE, are
mainly expressed at the acclimation phase. A study by White-Ziegler
et al. (2008) conducted a microarray analysis on E. coli K-12 MC4100
and demonstrated that approximately 7% of the genome (297 genes) exhi-
bited increased expression at low temperature (23°C) in comparison to their
optimal growth temperature of 37°C. Of those genes, 122 genes (41%) are
under the regulation of the general stress response rpoS. Proteins expressed
by the genes, otsA and otsB, respectively, revealed the synthesis of the
osmoprotectant, trehalose that plays a role in improving cell viability at cold
shock conditions. In particular, 107 genes (36%) were not specifically related
to any COG (Clusters of Orthologous Groups) functional group and
roughly 50% (149 genes) of the increased expressed genes at low tempera-
ture were either hypothetical or with unknown functions signifying the
need of more research to understand the adaptation of microorganisms to
low/cold temperature.
Responses to cold shock for Salmonella have been documented and char-
acterized to some extent. Using both global proteome and gene expression
profiling, Shah, Desai, Chen, Stevens, and Weimer (2013) identified the pri-
mary and significant genes expressed by Salmonella Typhimurium during
cold stress exposure as being cspA, cspB, cspC, cspD, and cspE, commonly
referred to as CSPs. Fifty-seven ribosomal-associated proteins were detected
in the profile analysis after the cold stress with 44 (77%) of the expressed pro-
teins persisting throughout cold stress. The genes recA and ssB that are
involved in recombination, SOS response, and repair, were among the genes
significantly expressed during cold stress. They are known to regulate the
expression of numerous genes of membrane biogenesis and transcription.
Other genes significantly induced due to cold stress belonged to various
functional groups, such as oxidative stress, amino acid transport and metab-
olism, tricarboxylic acid cycle, and complex I (NADH dehydrogenase of
electron transfer chain). Functions and details of the genes that most likely
contribute directly to cold shock will be discussed in the following sections
in general terms and where pertinent, Salmonella specifically.
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2.4 Cell Membrane Modification

The microbial cell membrane is the first cellular barrier of the external envi-
ronment. In general, the membrane consists mainly of fatty acids that adjust
and maintain membrane fluidity. Bacterial adaptation to cold shock/stress
produces some cellular changes at different levels from the cell membrane
that serves as an initial sensing barrier to the DNA encoding the genetic
information (Panoff et al., 1998; Phadtare, 2004; Shapiro & Cowen,
2012). A sudden temperature downshift leads to decreased membrane flu-
idity and as a result, disrupts its function. Under these conditions, the mem-
brane fluidity can revert from its liquid-phase state to more of a gel-phase
state if left unchecked. To retain membrane fluidity in response to cold
shock, Shivaji and Prakash (2010) stated that bacterial cells can change the
quantities of saturated and unsaturated fatty acids, modify the chain length
of fatty acids, adjust the cis to trans fatty acid and anteiso to iso fatty acid
proportionalities, as well as adjust membrane protein quantity and modify
concentrations of carotenoid types.
Marr and Ingraham (1962) observed an increase of unsaturated fatty acids
synthesis in cell membrane with fatty acid isomerization modifications when
E. coli was exposed to low temperature. The content of unsaturated fatty
acids is synthesized through three enzymes FabA, FabB, and FabF, of which
fabF is the main gene encoding a beta-ketoacyl-acyl carrier protein synthase
II with increased activity of Fabf at low temperature (Mansilla, Cybulski,
Albanesi, & de Mendoza, 2004). Sinensky (1974) also documented this
mechanism in E. coli and suggested a homeostatic process that regulates
the viscosity of membrane phospholipids (Chattopadhyay, 2006; Los &
Murata, 2004). The genetics of regulation of these alterations in desaturation
of membrane fatty acids has been characterized to some extent. Based on
their previous work with the cyanobacterium Synechocystis (Los, Horvath,
Vigh, & Murata, 1993; Vigh, Los, Horvath, & Murata, 1993), Los and
Murata (2004) have pointed out that the genetic control of the enzymes
involved in fatty acid desaturation appears to be responsive to the temperature
shift extent and not the absolute temperature. While fatty acid desaturation
mechanisms have been well documented, certain bacteria may emphasize dif-
ferent mechanisms to alter membrane composition in response to cold tem-
perature shock (Los & Murata, 2004).
Specific Salmonella cell membrane compositional changes in response to
cold temperatures have been documented as well. Wollenweber, Schlecht,
Luderritz, and Riftschel (1983) compared the fatty acid composition of the
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lipid A component of lipopolysaccharide in S. Typhimurium or S. Minne-

sota recovered after growth at either 37°C or 12°C under an aerobic atmo-
sphere in a complex medium. They identified the fatty acid and unsaturated
fatty acids in these serovars using gas–liquid chromatography and gas–liquid
chromatography/mass spectrometry, respectively. In response to the lower
temperature presumably as a means to alter membrane fluidity, the authors
observed a decrease in hexadecanoic and dodecanoic acids, the disappear-
ance of 2-hydroxytetradecanoic acid, and an increase in tetradecanoic acid,
accompanied by the emergence of a new fatty acid, palmitoleic acid in lipid
A mostly as a replacement of dodecanoic acid.
Growth phase and differences in membrane composition may be a factor
as well. For example, Kim et al. (2005) using gas chromatography/mass
spectrometry determined that cyclopropane fatty acids increased in S. Typ-
himurium upon initiation of stationary phase. By generating cyclopropane
synthase gene mutants which became acid sensitive, the authors demon-
strated that cyclopropane modification of the membrane phospholipids
imparted acid resistance to stationary phase S. Typhimurium. Whether such
modifications would elicit cold shock resistance in stationary phase Salmo-
nella would be of interest, particularly when food is stored at refrigeration
temperatures or frozen. It is conceivable since the Salmonella alternative
sigma factor RpoS which is generally induced as a stress-response gene acti-
vator during stationary phase influences cyclopropane fatty acid production
is also known to be involved in survival of Salmonella during refrigeration
particularly at high salt concentrations (Boor, 2006; Kim et al., 2005;
McMeechan et al., 2007).
2.5 DNA Supercoiling Modification

DNA characteristics (structure and shape) have an impact on DNA func-
tions. DNA supercoiling is the shape of DNA packed inside viable cells
in a very high DNA helix coiled with interwound supercoiling in prokary-
otic organisms. The state of DNA supercoiling can be either positive
“overtwist” or negative “unwind” (Mirkin, 2001). DNA supercoiling has
been shown to play numerous roles in genome functions with the resulting
changes in chromosomal topology generating a global impact on the respec-
tive gene expression in the corresponding bacterial cell (Cameron,
Stoebel, & Dorman, 2011; Dorman, 1991, 2006). It assures that DNA is
not damaged through the integration of DNA chains as a requirement for
replication, initiation, transcription, and recombination (Mirkin, 2001).
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DNA topoisomerases are the enzymes which function in all DNA-

associated topological states including DNA supercoiling. Negative DNA
supercoiling state is regulated by DNA gyrase and topoisomerase IV, while
positive DNA supercoiling is regulated by topoisomerases I and III (López-
Garcı́a, 1999; Terekhova, Gunn, Marko, & Mondragón, 2012). In each
DNA supercoiling state, the enzymes function to relax negative to positive
supercoiling and vice versa (Champoux, 2001).
As described in detail elsewhere (Cameron et al., 2011; Dorman, 1991,
2006; Hatfield & Benham, 2002; Travers & Muskhelishvili, 2005), DNA
supercoiling in pathogenic bacteria such as E. coli and Salmonella is exten-
sively influenced by environmental conditions. However, despite their sim-
ilarities, these two organisms do appear to differ in their DNA supercoiling
responses. Cameron et al. (2011) characterized DNA supercoiling in E. coli
and Salmonella enterica under exponential and stationary growth phase con-
ditions as well as their respective responses to osmotic stress and exposure to
novobiocin. Based on comparisons of the DNA topology of the two organ-
isms, the authors concluded that S. enterica was much less variable in chang-
ing the level of DNA supercoiling under these growth and environmental
conditions than E. coli. Furthermore, the FIS (factor for inversion stimula-
tion) protein that regulates DNA supercoiling exhibited less impact in
S. enterica than E. coli. The association of DNA negative supercoiling and
cold temperature has been previously demonstrated (Prakash et al., 2009;
Shivaji & Prakash, 2010). When DNA supercoiling increases in its negative
state, it indicates that DNA gyrase and topoisomerase IV were induced at
high levels to effectively maintain the cellular functions of DNA replication,
transcription, and recombination (Mizushima, Kataoka, Ogata, Inoue, &
Sekimizu, 1997; Shapiro & Cowen, 2012).
2.6 CIP Synthesis

When cells are shifted to cold temperatures, numerous proteins are
upregulated in response to the cold shock. They are designated as CSPs,
CIPs, and cold acclimatization proteins (CAPs). The first two groups can
accumulate and become associated with most of the housekeeping genes
being repressed following the cold temperature exposure. It has been
suggested that CSPs are small expressed proteins with sizes less than
10kDa and CSPs larger than that should fall within the CIP group. However,
CAPs are proteins characterized by very high synthesis occurring primarily
during extended exposure and subsequent growth at cold temperature
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(Hebraud & Potier, 1999; Neuhaus, Rapposch, Francis, & Scherer, 2000;
Panoff et al., 1998; Phadtare, 2004; Polissi et al., 2003).
CSPs are small response proteins involved in several molecular functional
activities, such as DNA replication, transcription, translation, and other
mechanisms yet to be identified (Golovlev, 2003). Collectively, they are
referred to as nucleic acid chaperones and they essentially act to inhibit
secondary RNA structure formation (Barria et al., 2013). These proteins have
been identified as being conserved in numerous Gram-positive and -negative
bacteria sharing a similarity of more than 45% with CSP families with some
consisting of up to nine members. In some bacteria, these csp genes are orga-
nized in chromosomal clusters (Neuhaus, Francis, Rapposch, G€ org, &
Scherer, 1999; Wouters et al., 1998; Yang et al., 2009). Other cold-associated
proteins, CIPs vary in numbers from bacterial species to another, and Barria
et al. (2013) have summarized a list of these proteins along with functions in
their review. Over 25 cold-induced genes have been described previously
(Barria et al., 2013; Phadtare & Severinov, 2010). The following sections will
briefly touch on some of these proteins and which have been characterized
in Salmonella.
2.6.1 Cold Shock Proteins

Cold shock genes generate a group of proteins, collectively designated as
Csp proteins, some of which have been better characterized from a func-
tional standpoint than others. Based on these in-depth characterizations,
definitive cold shock mechanistic properties can be established that conform
with what is generally known about bacterial responses to cold shock at the
cellular level. In E. coli, the Csp group consists of nine known proteins with
genes for proteins CspA, CspB, CspG, and CspI being considered cold
shock inducible (Bae, Xia, Inouye, & Severinov, 2000; Giuliodori et al.,
2010; Yamanaka, Fang, & Inouye, 1998).
The CspA protein is considered the most extensively studied of all CSPs,
and much of what is known is based on studies with E. coli. The protein
consists of 70 amino acids and can bind either single-stranded DNA or
mRNA, thus acting as a gene-expression regulator potentially impacting
both transcriptional and translational properties of the bacterial cell. In addi-
tion, it possesses the ability to bind mRNA by acting as a chaperone, thus
forcing RNA into a single-stranded form, and subsequent degradation
(Barria et al., 2013). Two genes, gyrA and hns, are transcriptionally activated
by CspA by stabilizing the RNA polymerase (Jones, Krah, Tafuri, & Wolffe,
1992; La Teana et al., 1991; Panoff et al., 1998). GyrA and H-NS have
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previously been demonstrated to be involved in the negative DNA super-

coiling (Gualerzi et al., 2003; Phadtare & Severinov, 2010; Stella, Falconi,
Lammi, Gualerzi, & Pon, 2006). Early work by Fang, Jiang, Bae, and Inouye
(1997) using mutational substitution analyses of the cspA gene in E. coli dem-
onstrated that the cspA gene is constitutively transcribed at 37°C, but the
resulting RNA is unstable at the higher temperature, thus preventing trans-
lation into a functional protein. Instead, cspA RNA becomes stable as the
temperature is lowered to 37°C and resulting in a fully functional CspA pro-
tein (Fang et al., 1997). In more recent studies, Giuliodori et al. (2010)
expanded on this concept of changes in RNA structural integrity by dem-
onstrating that the cspA mRNA structures were not only different at 37°C
compared to their corresponding counterparts at cold temperatures, but
that this was probably due to stabilization of an RNA intermediate at the
low temperature. In addition, they were also able to show that the cspA
mRNA was more efficiently translated at the colder temperatures. As an
overall conclusion, they proposed that the cspA mRNA served as some form
of thermosensor that could detect temperature downshifts and contained
components that improved translational efficiency at these lower temper-
atures. Bae et al. (2000) demonstrated that CspA-family proteins also
function as CSPs at the transcriptional level by serving as transcription ant-
iterminators. Using a combination of in vitro addition of the respective Csp
proteins and in vivo overexpression of cloned Csp proteins in E. coli incu-
bated at 37°C, they concluded that CspA, CspC, and CspE could induce
transcription of nusA, infB, rbf, and pnp genes via antitermination, thus
suggesting that cold shock activation of these genes occurs by transcription
antitermination.
Salmonella possesses several of the Csp proteins known to occur in E. coli,
and some of these have been characterized. Jeffreys, Hak, Steffan, Foster, and
Bej (1998) noted that S. Enteritidis could survive freezing temperatures for
increased periods of time if initially exposed to 10°C. Further characteriza-
tion by Jeffreys et al. (1998) using Western blotting with an E. coli CspA anti-
body and identification of radiolabeled proteins in cold shocked S.
Enteritidis led to the isolation of a protein that was similar in size and pro-
moter nucleotide sequences as its counterpart in E. coli. However, the
authors concluded that sufficient differences in sequences in other regions
of the gene could explain its expression in S. Enteritidis under less stringent
temperatures. In a follow-up study with S. Typhimurium using similar
approaches, Horton, Hak, Steffan, Foster, and Bej (2000) identified a CspA
protein in this serovar as well, but unlike S. Enteritidis induction required a
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substantial decrease in temperature for induction of the S. Typhimurium

cspA gene to occur. Salmonella serovar differences in responses to stresses
and other physiological functions are not surprising and have been noted
when different serovars and in some cases even the individual strains of the
same serovar are exposed to certain environmental conditions or exhibit dif-
ferent infectious phenotypes (Andino & Hanning, 2015; González-Gil et al.,
2012; Heithoff et al., 2012; Ricke, 2017; Shah, 2014; Shah et al., 2012).
Other Csp proteins have been identified and characterized in Salmonella.
Craig, Boyle, Francis, and Gallagher (1998) constructed a series of S. Typ-
himurium Mudlux gene fusion insertion mutants and isolated a series of lux
expression mutants that were luminescent at different rates as the tempera-
ture was dropped from 30°C to 10°C. From this set of mutants one mutant
was isolated that responded with a high level of induction at 10°C and was
identified as cspB next to the umuDC operon. Further characterization rev-
ealed that luminescence could only be detected at 22°C or below and the
cspB mRNA proved to be stable at 10°C but destabilizes as the temperature
was increased. This is consistent with the later observations made for E. coli
cspA mRNA and corresponds to an RNA-based thermal sensing role for
these the mRNA generated from these csp genes.
Not all Csps in Salmonella exhibit this pattern. For example, Kim et al.
(2001) examined the expression of the cspH gene in S. Typhimurium and
found that it was activated at 37°C and its mRNA was more stable than
other csp mRNAs at this temperature. They confirmed this with cspH–lacZ
gene fusion constructs that demonstrated that lacZ expression was also
induced at 37°C. Based on these results, they concluded that the S. Typ-
himurium cspH gene possesses a broad temperature range (30–10°C) for
induction and can respond to relatively small changes in external tempera-
ture. In a follow-up study Kim et al. (2004) further demonstrated that
cspH induction occurred during early log phase growth. They observed
an increase in cspH when stationary phase S. Typhimurium cells were given
a nutrient upshift at 37°C, but not in the presence of a gyrase inhibitor or in
a fis-deficient mutant. More recently, Morgan, Wear, McNae, Gallagher,
and Walkinshaw (2009) structurally characterized the CspE protein from
S. Typhimurium by crystallizing purified protein and conducting X-ray
crystallography analyses of the protein structure. The authors concluded that
the three-dimensional model of the S. Typhimurium CspH protein ana-
lyzed in their study proved to be similar to the structure of other previously
characterized Csps.
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2.6.2 CsdA
Cold-shock DEAD box protein A (CsdA), previously known as “DeaD,” is
one of five members of the DEAD-box family, a branch of the helicases
superfamily 2 (Kaberdin & Bl€asi, 2013). This protein is involved in several
cellular mechanisms, including ribosome biosynthesis, translational initia-
tion, and mRNA decay by stabilizing the cspA mRNA for the major cold
shock protein A (CspA). During cold shock conditions, it binds the
RNA degradosome with RNase E and is required for riboregulation of rpoS
mRNA (Horne, Kottom, Nolan, & Young, 1997; Kaczanowska & Ryden-
Aulin, 2007; Peil, Virum€ae, & Remme, 2008; Shajani, Sykes, & Williamson,
2011; Weber & Marahiel, 2003).
Limited work on CsdA has been conducted on Salmonella. Li, Meng,
Wang, and Sun (2012) used an mRNA differential-display reverse
transcription—polymerase chain reaction (PCR) approach to screen for
genes involved in viable nonculturable (VBNC) Salmonella Pullorum. Their
interest stemmed from the need to detect this particular serovar in its VBNC
state because of its poultry infection capability even when it was not recov-
erable in traditional culturing methods. They transferred 37°C grown S.
Pullorum cells into medium held at 4°C to generate VBNC physiological
state and used mRNA differential amplification to screen for cDNA frag-
ments only present in the VBNC cells. Based on sequence analyses of the
isolated cDNA that was unique to the VBNC cells they aligned this fragment
with an ATP-dependent RNA helicase rh1B gene and contained conserved
regions of the DEAD-box helicase. They concluded that the rh1B gene
potentially functioned in cold shock survival in a similar manner as the
DEAD-box RNA helicases described previously by Cordin, Banroques,
Tanner, and Linder (2006). Their proposed use of this gene as a marker
for detection of VBNC S. Pullorum could potentially be applied to
foodborne Salmonella that are in a VBNC physiological state during refrig-
eration or frozen storage.
2.6.3 NusA
The NusA protein is a component of an antitermination complex and induced
earlier at DNA transcription to bind RNA polymerase and influences pausing
and/or termination of transcription. It also influences transcriptional
antitermination and stabilizes the RNA polymerase process. It was identified
to be induced under cold temperature conditions (Bae et al., 2000; Mah,
Kuznedelov, Mushegian, Severinov, & Greenblatt, 2000). In Salmonella,
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the NusA protein may impact pathogenesis as well. Van Immerseel et al.
(2008) used transposon mutagenesis to identify S. Enteritidis genes potentially
involved in direct or indirect transcriptional regulation of the hilA gene that
encodes the transcriptional activator of Salmonella Pathogenicity Island-1 and
nusA was identified as one of the genes that impacted hilA expression. They
noted that deletion of the nusA gene caused reduction in hilA expression and
they speculated that this could have resulted from the inefficient HilA protein
translation or of the hilA regulators but the interactions of other potential fac-
tors precluded definitive conclusions.
2.6.4 DnaA
The dnaA gene which encodes for DnaA protein is considered a cold-
inducible protein and possesses both DNA binding/replication initiator
properties and acts as a global regulator of transcription (Barria et al.,
2013; Gualerzi et al., 2003). The DnaA protein is centrally involved in the
initiation of chromosomal and mini-chromosomal DNA replication on oriC
and appears to be important in the timing control of cell-cycle initiation
(Atlung, Clausen, & Hansen, 1985; Messer & Weigel, 1997). It also
autoregulates the dnaA gene and influences cell membrane structural properties
(Atlung et al., 1985; Atlung & Hansen, 1999; Braun, O’Day, & Wright, 1985;
Kaguni, 2006; Messer & Weigel, 1997; Wegrzyn & Wegrzyn, 2002; Węgrzyn,
Wrobel, & Węgrzyn, 1999). Messer and Weigel (1997) have summarized the
role of DnaA protein as a transcription factor which depending on the target
gene promoter location can serve as a transcriptional activator, repressor, or
terminator. Atlung and Hansen (1999) concluded that DnaA was involved
in cold shock after demonstrating the levels of DnaA protein when E. coli
was shifted from 37°C to 14°C were twofold higher even though there were
indications some of the synthesized protein was irreversibly inactive or that all
present at the lower temperature generally exhibited irreversible low activity.
Less is known about DnaA in Salmonella, but when the dnaA sequences were
compared between E. coli and S. Typhimurium they were relatively homol-
ogous and functionally were presumed to behave in a similar fashion by the
authors (Skovgaard & Hansen, 1987). Further work on regulatory mechanisms
associated with Salmonella dnaA has been done more recently. When Dadzie
et al. (2013) conducted transcriptomic deep sequencing profiles of S. Typhi
they identified a cis-encoded antisense RNA expressed primarily during sta-
tionary phase and contributed to the stability of dnaA mRNA. Expression
of this antisense RNA was also observed in the presence of iron limitation
and osmotic stress but cold shock was not examined in this study.
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2.6.5 RecA
When Shah et al. (2013) exposed S. Typhimurium to 5°C cold stress, they
detected induction of the RecA protein. RecA is considered a CSP that is
involved in the recombination and the SOS response for DNA repair (Barria
et al., 2013; Gualerzi et al., 2003; Jones & Inouye, 1994). The SOS response
occurs when RecA inactivates LexA and as a result over 31 genes are
upregulated. In addition, the elevated amount of active RecA in the cyto-
plasm can associate them with the membrane (Han & Lee, 2006; Lee &
Lee, 2003). RecA is also essential for flagellar-driven swarming behavior
in E. coli and Salmonella (Gomez-Gomez, Manfredi, Alonso, & Blazquez,
2007; Mayola et al., 2014; Medina-Ruiz et al., 2010). Mayola et al. (2014)
in a series of mutant fusion studies along with microfluidic and chemotaxis
capillary assays established a direct link between S. Typhimurium RecA,
chemotaxis, and flagellar rotation switching. This led them to suggest that
Salmonella RecA is involved in swarming and chemotaxis. Whether Salmonella
swarming behavior and flagellar motion would be influenced by changes in
RecA production during cold shock is not known, but Shah et al. (2013)
did not observe an intense-induction response of the S. Typhimurium CheY
protein (flagellar rotational regulator) in response to cold stress.
2.6.6 Trigger Factor

The trigger factor (TF) protein in E. coli (peptidyl prolyl isomerase) has been
identified as a molecular chaperone to correct protein folding and hydrolyze
misfolded polypeptides (Phadtare, 2004). The tig gene is induced by multiple
stresses and is involved in ribosome binding. It is induced under cold shock
conditions and has a role in improving the cellular viability of E. coli when
temperature falls between 4°C and 16°C where the level of TF protein
increases significantly (Kandror & Goldberg, 1997). In addition, the protein
is involved in cotranslational proteins folding and sustains the exportation of
proteins in a structurally efficient state through the support of the cold-
damaged proteins refolding (Barria et al., 2013; Han & Lee, 2006;
Phadtare & Severinov, 2010). Shah et al. (2013) observed considerable
induction of the tig gene which encodes TF in S. Typhimurium during
cold-stress exposure. However, Di Pasqua, Mauriello, Mamone, and
Erclolini (2013) using quantitative reverse transcription—PCR observed
reduced expression of tig in S. Thompson and downregulation of the TF
protein upon exposure to 15°C leading them to suggest that this cold accli-
mation protein was not involved in cold-stress adaptation. It is possible that
TF is less important for cold-stress adaptation in some Salmonella serovars
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than others given the serovar differences know to occur in genetic responses
to other stresses (Andino & Hanning, 2015; González-Gil et al., 2012).
There may be a temperature gradient impact as well since Shah et al.
(2013) used 5°C cold shock vs 15°C by Di Pasqua et al. (2013). More quan-
titative comparisons need to be made across serovars to assess whether TF is
serovar specific for cold stress responses and examined over a range of incre-
mental cold temperature differences.
2.6.7 RbfA
Ribosome-binding factor A is a CSP that is essential for efficient translation
(16S rRNA processing and 30S ribosomal subunit) and cell growth at cold
temperature (Barria et al., 2013). The RbfA protein initially was character-
ized as a multicopy suppressor of a cold sensitive 16S rRNA mutation
(Dammel & Noller, 1995; Weber & Marahiel, 2003). The rbfA mRNA
has a section containing an A/T rich sequence downstream where the start
codon is known as a translation-enhancing element. In cold-shock mRNAs,
it has been recognized as a translation initiation enhancement factor (Barria
et al., 2013; Kaczanowska & Ryden-Aulin, 2007; Phadtare & Severinov,
2010; Qing, Xia, & Inouye, 2003; Shajani et al., 2011).
2.6.8 PNPase
This enzyme, polynucleotide phosphorylase (PNPase), is encoded by the pnp
gene (Phadtare & Severinov, 2010). It is a major E. coli degradosome ele-
ment with a 30 -to-50 exonuclease mainly involved in RNA metabolism.
PNPase activity has been demonstrated to be significantly essential at
cold-induced conditions for cell survival and growth (Haddad et al., 2009;
Hu, McCormick, Means, & Zhu, 2014; Mathy, Jarrige, Robert-Le
Meur, & Portier, 2001). In addition, it is induced at a posttranscriptional stage
and is autoregulated with a role in inhibiting translation and stabilizing
mRNA. Furthermore, it suppresses the CSPs family production at the end
of the acclimation phase (Barria et al., 2013; Kaberdin & Bl€asi, 2013;
Phadtare & Severinov, 2010). In addition to cold adaptation, the PNPase
protein may have additional functions in Salmonella (Clements et al., 2002;
Ygberg et al., 2006). For example, Clements et al. (2002) used mouse studies
and microarray analyses to demonstrate that S. Typhimurium PNPase
impacted pathogenicity islands 1 and 2 virulence genes, altering acute vs per-
sistent infection and negatively controlling spv virulence gene expression
(Ygberg et al., 2006). More recently, it has been shown by Bearson,
Bearson, Lee, and Kich (2013) to also be required for S. Typhimurium col-
onization of swine.
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2.6.9 KsgA
The KsgA protein is a dimethyl adenosine transferase (a 16S rRNA adenine
methyltransferase in E. coli). The ksgA gene is critical at cold-induced tem-
peratures for cell growth rate and is a regulator of ribosome biogenesis
(Kaczanowska & Ryden-Aulin, 2007; Shajani et al., 2011; Zhang-
Akiyama et al., 2009). While KsgA appears to be important in cold adapta-
tion for E. coli, Chiok, Addwebi, Guard, and Shah (2013) did not detect an
impact on growth response in a KsgA deficient S. Enteritidis mutant when
exposed to suboptimal temperature, and this mutant did not appear to
exhibit a cold-sensitive phenotype. However, these authors did observe
increased susceptibility to high osmolarity, chloramphenicol, oxidative stress
in this mutant and they concluded that KsgA might play a role in intestinal
colonization and organ invasion of chickens. Whether similar responses
occur in other Salmonella serovars remain to be determined.
2.6.10 SrmB
The SrmB protein is a member of the DEAD-box family of the helicases
superfamily 2 (Kaberdin & Bl€asi, 2013; Khemici & Linder, 2016). It was first
isolated by Nishi and Schnier (1986, 1988). It plays a role in ribosome bio-
genesis mainly for the assembly of the 50S ribosomal subunit. It has been
shown that SrmB is involved at the ribosomal biogenesis level in advance
of CsdA. At cold temperatures, it causes a defect in cell growth when deleted
and is overexpressed in the wildtype strain of E. coli. In addition, it was pro-
posed that this protein possibly operates as an ATP-independent RNA
chaperone (without the energy source of ATP hydrolysis) and interacts with
23S ribosomal RNA subunit (Kaczanowska & Ryden-Aulin, 2007;
Phadtare & Severinov, 2010; Shajani et al., 2011). In their review,
Khemici and Linder (2016) concluded that it needs to be worked out before
fully understanding the molecular functioning of these DEAD-box proteins.
If and/or how Salmonella utilizes these DEAD-box family of helicase pro-
teins such as SrmB during cold shock remains to be determined.
2.6.11 Initiation Factors (IFs)

The initiation factor 2, encoded by the infB gene is involved in the initiation
of bacterial translation with GTPase activity (Jones, VanBogelen, &
Neidhardt, 1987; Laursen, Sørensen, Mortensen, & Sperling-Petersen,
2005). This protein in concert with two other factors, IF1 and IF3, directs
the selection of the 30S subunit of initiator tRNA and mRNA translation
initiation region to form the “30S preinitiation complex” and initiates the
process (Laursen, Mortensen, Sperling-Petersen, & Hoffman, 2003).
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Laursen et al. (2005) have stated that all three translation initiation factors
could be involved in cold shock regulation based on data summarized by
Gualerzi et al. (2003) that indicated a doubling of their stoichiometry with
respect to the ribosomes during cold shock exposure. Upregulation of IF2
has been reported for cold shocked E. coli and was proposed to result from
CspA and the other cold shock-induced Csp protein’s ability to facilitate
transcription antitermination (Bae et al., 2000; Laursen et al., 2005).
Presumably, Salmonella IFs would behave in the same fashion, but this has
not been clearly established. Early work using an immunoblotting approach
to compare E. coli with S. Typhimurium suggested that IF2 and IF3 were
structurally similar between the two bacteria (Howe & Hershey, 1984).
More recently, Pavlov, Zorzet, Andersson, and Ehrenberg (2011) compared
IF2 amino acid sequences between S. Typhimurium and E. coli and reported
that they were greater than 96% identical and behaved nearly the same in the
in vitro initiation translation system they used for their studies. Shah et al.
(2013) reported some increase in expression of the S. Typhimurium infC
gene product (encodes IF3 protein) under cold shock conditions, particu-
larly late in the incubation period when compared to noncold shock con-
ditions. As is the case with other CIPs, more definitive work will need to
be done with other Salmonella serovars in the presence of cold temperatures
to elucidate how universal these cold shock response systems are in
Salmonella.
3. SALMONELLA–COLD SHOCK INTERACTION WITH

OTHER STRESS RESPONSES
3.1 Cross-Protection
During food processing, foodborne pathogens are exposed to numerous
stresses that possibly have a major influence on microbial global stress systems
and at least in some cases lead to adaptation where the organism becomes
more virulent and/or resistant to multiple stressors (Archer, 1996). Conse-
quently, depending on the interventions being employed it may become
possible for a foodborne pathogen to experience cross-protection when it
becomes tolerant/resistant to multiple hurdles and become a challenge for
the food industry to control (Ricke et al., 2005). It has been confirmed
in a variety of research studies over the years that an improvement in toler-
ance and resistance of a microorganism can occur when they are exposed to
other subsequent stresses (Rangel, 2011).
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The development of cross-protection in Salmonella is known to occur in

the presence of cold temperatures. For example, in a study by Xu, Lee, and
Ahn (2008), the authors evaluated the cross-protective capacity of acid-
adapted S. Enteritidis strain to resist cold stress and concluded that acid-
shocked cells for a period of 2 h were more resistance to cold stress than a
longer acid shock for 7 h. In addition, they observed that acid-adapted
S. enterica cells can be present in the VBNC state that requires the resusci-
tation for the transition to the culturable state. This outcome could very well
have physiological significance as acids are extensively applied in the food
industry both directly as antimicrobial preservatives and generation of
organic acids via fermentation of various food products (Ricke, 2003b).
Previously, it has been shown that S. Typhimurium upon prior exposure
to organic acids can become tolerant to inorganic acid shock as well as non-
acid stressors such as hydrogen peroxide and high osmolarity (Kwon, Park,
Birkhold, & Ricke, 2000; Kwon & Ricke, 1998).
A more recent study by Shah et al. (2013) simulated the conditions by
which Salmonella cells are exposed to cold temperatures used in storing foods
and subsequently consumed followed by exposure to acidic–gastric condi-
tions. They tested the response of S. Typhimurium LT2 strain for various
stresses (peroxide, osmotic, and acid (pH 5.3) for a time period of 30 min
(shock) and 5 h (stress)). They noted that only peroxide shock critically
decreased cellular survival indicating a potential capacity of this foodborne
pathogen to endure harsh environmental stresses for several hours mainly
during transit and inside the host. Proteomic profiles indicated that 104 pro-
teins were expressed during exposure to cold stress. They were divided into
three categories as information storage and processing, cellular processing,
and metabolism.
3.2 Interaction With Virulence Responses

In addition to cross-protection to other antimicrobials, exposure to certain
environmental stressors associated with the food industry can also lead to
enhanced pathogenesis (Archer, 1996). One of the earliest studies conducted
in evaluating the pathogenicity of Salmonella after freezing was by Sorrells,
Speck, and Warren (1970). They used a S. Gallinarum cell suspension and
froze it at 75°C in a bath of dry ice acetone followed by storage at 20°C
for 1 day. This treatment yielded three kinds of cells, dead, metabolically
injured, and undamaged cells. They compared freezing the cell suspen-
sion at 75°C as the sole condition and after storage at 20°C for 1 day.
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They evaluated the pathogenicity of uninjured and frozen sublethally

injured cells by injecting a 1 mL cell suspension into the peritoneum (the
body cavity) of 6-week-old chicks (180 chicks, 18 groups, 10 chicks in each
group). They concluded that the differences between the two treatments
were not statistically significant. This demonstrated that metabolically
injured cells after preservation by freezing were capable of recovering when
conditions were favorable and could potentially cause infections (Sorrells
et al., 1970).
The process of causing an infection is complicated and involves several
steps in bacterial pathogenesis. Critical steps of infection are adherence and
invasion to host cells. Two main bacterial adhesions are fimbriae (pili) (type
1, P, and S fimbriae) and afimbrial adhesion. Afimbrial adhesins are proteins
that play a role in colonization as adherence factors but differ in not forming
a long structure such as fimbrial adhesions (Wilson et al., 2002). Cold stress
has been shown to enhance the association between S. Typhimurium and
Caco-2 epithelial cells through adhesion and invasion (Shah, Desai, &
Weimer, 2014). Cold stress induced the gene expression of numerous genes
associated with virulence such as Type III Secretion Systems (T3SS) and
their effectors for SPI-1 and SPI-2. Other induced genes belong to cell pro-
cesses (pathogenesis and DNA transformation), prophage functions, plasmid
functions, protein secretion and trafficking, DNA replication, recombina-
tion and repair, purine ribonucleotide biosynthesis, and RNA degradation.
Virulence effectors can be directly exported into the cytoplasm of the
host cell via T3SS (also referred to as the injectisome) in Salmonella as well
as various Gram-negative bacteria such as E. coli, Shigella, Vibrio, and Yersinia
(Tsai, Burkinshaw, Strynadka, & Tainer, 2015). The SPI-1 and SPI-2 that
encode for T3SS are the main factors of Salmonella pathogenesis. Virulence
of Salmonella depends on SPI-2 T3SS for translocation of effector proteins to
host cell from vacuolar-resident bacteria (Jennings, Thurston, & Holden,
2017). Hapfelmeier et al. (2005) reported attenuated colitis from Salmonella
mutants having only an SPI-1 (M556; sseD::aphT) or SPI-2 TTSS (SB161;
ΔinvG) (Hapfelmeier et al., 2005). Some genes associated with SPI-2 T3SS
are located outside SPI-2 in SPI-5 are necessary for intracellular replication
of Salmonella during enteric infection. A set of genes that creates part of the
Type IV Secretion System (T4SS) is expressed in response to cold stress. The
function of these genes is essential as part of plasmid function and conjugal
DNA transformation.
Shah et al. (2014) examined the effect of cold exposure 5°C for 48 h on S.
Typhimurium pathogenicity by quantifying adhesion and invasion of
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Caco-2 cultured tissue cells. They observed increases in both adhesion and
invasion of the Caco cells after exposure to the cold stress conditions. In con-
junction with the tissue culture assays, the authors also conducted gene
expression profiles and noted induction of several groups of virulence genes
as well as metabolic genes in response to cold stress. The virulence genes
included T3SS-associated genes located on the Salmonella pathogenicity
islands. Assessment of Salmonella gene expression in infected Caco cells rev-
ealed induction of intracellular proliferation genes, spvR and spvABC and
several stress-related genes including the cold shock genes cspABE. This
together with their previous research (Shah et al., 2013) where they reported
that cold stress also induced acid resistance, led them to suggest that cold
stress could, in fact, increase overall pathogenicity in Salmonella. It is con-
ceivable that such prior exposure might lower the infectious dose for Salmo-
nella and thus enhance risk. This in part would depend on how sustained
induction and presence of CSPs would be once Salmonella is removed from
the cold environment of the chilled food matrix during consumption and
ingestion. Whether this would be a practical consideration to take into
account for screening Salmonella physiological status and upshifts of CSPs
remains to be determined. Presence and significance of Salmonella in frozen
and chilled foods will be discussed in the following section.
4. SALMONELLA RESPONSES TO COLD TEMPERATURES

IN FOOD PRODUCTION
4.1 Salmonella Growth, Survival, and Influential Factors
Freezing and chilling (refrigeration) are common methods of food preserva-
tion by lowering the temperature of food products affecting several func-
tional mechanisms of microorganisms including metabolism (Archer,
2004). As newer food cold temperature preservation technologies have been
developed, this will no doubt impact Salmonella growth and survival under
these conditions and further complicate attempts to delineate the mecha-
nisms associated with these environmental stressors. Some of these preserva-
tion approaches involve combinations that alter the food environment in
multiple ways. For example, application of rapid vacuum cooling in food
processing involves rapid evaporative decreases in temperature and removal
of moisture and has been mostly applied to horticulture products
(McDonald & Sun, 2000). Likewise, as suggested by Russell (2002) the
combination of chilling with bacterial membrane disrupting technologies
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such as ultrasound, high hydrostatic pressure, or pulsed electric field are

potential means to further extend shelf life.
Over the past few decades, several fundamental studies of Salmonella sur-
vival/injury/growth involving freezing and chilling have been conducted.
Most of the early research involved enumerating the recoverable bacterial
cell populations after exposure to different cold temperatures and/or differ-
ent periods of times of exposure to a particular temperature. For example,
Sorrells et al. (1970) found that the freezing condition of 75°C resulted
in 86% cell death and 29% of S. Gallinarum survivors becoming injured
cells, whereas storing the cell suspension at 20°C for 1 day after freezing
at 75°C increased the death rate by 2% (total of 88%) and resulted in 13%
additional injured cells (total of 42%) of the survivors.
In more recent research by M€ uller et al. (2012), they investigated the
ability of some Salmonella clones from stationary- and exponential-phases
to survive and grow after exposure to freezing stress (mimicking a meat
processing chain) for up to 48 weeks in minced pork meat. Salmonella strains
were selected using a mathematical model for epidemiological studies and
characterizing the selected isolates to be either a successful or nonsuccessful
clone. Twenty-six Salmonella isolates were selected with different antimicro-
bial resistance characteristics belonging to 6 serovars (14 strains S. Typ-
himurium, 4 strains S. Derby, 2 strains S. Newport, 2 strains S. Infantis,
2 strains S. Saintpaul, and 2 strains S. Virchow) from human and animal
sources. The study concluded that up to 1 log reduction of cells at stationary
phase of all strains was observed after 1 year of frozen storage, while more
than a 1 log decrease of cells occurred during the exponential growth phase
for the two strains of S. Typhimurium that exhibited the same reduction in
49 days of freezing stress indicating that exponential phase cells have more
sensitivity to the same stress (M€
uller et al., 2012). They evaluated the recov-
ery time needed by observing the growth in lag phase after the freezing stress
for stationary and exponential phases of S. Typhimurium strains. The initi-
ation of growth acquired an average of 102 min for stationary phase cells and
shorter than that for cells of exponential phase (M€ uller et al., 2012).
Phillips, Humphrey, and Lappin-Scott (1998) investigated the effect of
chilling on two S. Enteritidis PT4 strains, E and I with strain E being more
tolerant and pathogenic. These strains were considered different in heat- and
acid-tolerance with the ability to survive on surfaces, and pathogenicity in
animal models. For both strains, stationary phase cells were diluted to cor-
respond to 5 105 mL1 and were used for chilling at 4°C for 12 days. The
results indicated that strain I was consistent at all time periods and did not
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exhibit any significant reductions, whereas strain E expressed significant

reduction at day 12. At the end of the treatment, strain E exhibited a sub-
lethal injury (metabolic and structural injury) of 93%, while 29% occurred in
strain I (Phillips et al., 1998). Therefore, even strains from the same species
can potentially respond to stresses differently as has been seen in the response
of Salmonella to other stresses (Andino & Hanning, 2015).
Several microbial factors can influence the subsequent assessment of
microbial responses to freezing. As discussed by Archer (2004) such factors
include the growth phase of the organism, rate of freezing, and recovery
media used for estimating viable microbial survivors. In addition, as
Archer (2004) points out the composition of the menstruum which the
microorganism is associated with while exposed to cold shock can be a fac-
tor, depending on the presence of compounds that exhibit cryobiological
properties. It is well known that compositional differences can play a role
as protective factors for pathogens when subjected to other stressors such
as thermal or acid (Jarvis et al., 2016; Waterman & Small, 1998) and there-
fore it should be no surprise that similar interactions occur for cold shock as
well. For example, Smadi, Sargeant, Shannon, and Raina (2012) using
mixed effect meta-analysis, demonstrated a statistically significant difference
when a chicken meat matrix was used vs laboratory media to assess Salmonella
growth at refrigeration temperatures. Consequently, it may be important to
assess quantitative impacts of cooling and freezing in matrices that approx-
imate the actual food product as closely as possible to achieve the best esti-
mates of responses in food processing.
However, not all differences in food products are solely due to food
composition alone. For example, Aldsworth, Sharman, Dodd, and
Stewart (1998) demonstrated that the presence of viable non-Salmonella
microbiota protected the underlying S. Typhimurium against freeze injury
by changing the oxygen tension through respiration of the competitive
microbial population. This protective outcome would suggest that micro-
bial population differences in different foods and, in some cases, the same
food source could contribute to differences in Salmonella survival during cold
shock. It would be interesting to follow Salmonella survival during extended
cold storage as the non-Salmonella population shifts to a more cold-tolerant
psychrotrophic microbiota (Dainty & Mackey, 1992).
Cold preservation of foods continues to be an important component of
the food supply system in the United States. As of early 2018, cold storage
supplies of frozen poultry and red meats in the United States were increased
from the previous month and poultry was increased 13% from the year
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before (USDA Cold Storage Report, 2018). In this same report, frozen pork
supplies were up 16% from the previous month, while frozen fruit and veg-
etable stocks were decreased compared to the month before. Regardless of
the food commodity, storage under cold conditions is a potential risk for
long-term carryover of Salmonella if the product has become contaminated
at some point during processing of the food. The following sections describe
a select set of studies conducted on the various food commodities involving
chilling or freezing and Salmonella responses that illustrate some fundamental
factors that need to be considered.
4.2 Beef Products

A simulation study of commercial freezing was used for beef trimmings
and three Salmonella serotypes (S. Brandenberg, S. Dublin, and S. Typ-
himurium) for exposure to slow (18°C) and rapid (35°C) freezing rates
reaching a temperature of between 17°C and 22°C within 24 h incuba-
tion (Dykes & Moorhead, 2001). The rate exhibited by rapid freezing was
1.8 times more rapid. Subsequently, all treated beef trimmings were stored at
18°C for 9 months. Monthly samples were collected after thawing and ref-
reezing, plated on selective and nonselective media, and Salmonella strains
enumerated. Beef trimmings samples were partially thawed and refrozen
at 18°C for 24 h to evaluate the potentially stressful procedure on the Sal-
monella serotypes. The survival difference of all strains was not significant as
expected during the storage time period (Dykes & Moorhead, 2001). Their
explanation was that the inoculated strains were rapidly frozen compared to
the meat. In addition, no significant sublethal cell injuries were determined
after comparing cell counts on selective and nonselective media.
Long-term refrigeration studies have been conducted on beef as well.
For example, Pittman et al. (2011) examined the potential to combine citrus
essential oils with refrigeration on beef subprimal cuts (brisket flats) using
a surrogate generic 5 strain biotype I E. coli cocktail that behaved similarly
to pathogenic E. coli O157:H7 and Salmonella species when growth and
survival responses were compared. Once inoculated with E. coli, brisket
samples treated either with no spray, water spray control, 3% oil, or 6%
oil were held in 4°C cold storage over a 90-day period and E. coli were
enumerated on days 1, 2, 3, and 5, followed by 5-day intervals from day 5
to day 90. The citrus essential oil treatment significantly reduced E. coli on
the brisket over the entire refrigeration storage period when compared to
the no spray and water spray controls. Based on unpublished work, the authors
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did not observe a difference in minimum inhibitory concentration of essential

oils between 4°C and 37°C. The authors suggested that synergism did not
occur between temperature and the citrus essential oil but that the essential
oil compound retained its antimicrobial activity at the lower temperature.
4.3 Chicken Meat Products

Dominguez and Schaffner (2009) conducted a study on Salmonella survival
in processed chicken products stored under frozen conditions. A cocktail of
Salmonella strains, S. Kentucky and S. Typhimurium, originally isolated
from chicken, with and without antibiotic resistance, were inoculated in
fully cooked chicken nuggets and uncooked (raw) chicken strips; subse-
quently, the inoculated products were stored in a laboratory freezer
(20°C) for 16 weeks with a weekly sampling collection. Samples were ana-
lyzed and plated in minimal, selective, and nonselective media. After incu-
bation for 24 h at 37°C, colonies were enumerated to determine the
survival of the bacterial cell population. The results demonstrated that
Salmonella strains are capable of surviving freezing food processing for long
periods of storage time when using frozen processed chicken products
(Dominguez & Schaffner, 2009).
Chaves, Han, Dawson, and Northcutt (2011) conducted a study to
determine the survival of S. Typhimurium artificially inoculated on the sur-
face of raw poultry products, skinless chicken breasts, and chicken thighs
with skin, treated with freezing (85°C for 20 min). Late exponential-phase
cultures were cold-shocked at 4°C incubated for 10 days, and noncold
shocked cultures were used to inoculate skinless chicken breasts and chicken
thighs with skin. For the crust freezing treatment, samples were divided into
two groups. One group was crust frozen at 85°C for 20 min and the other
group was frozen at 85°C for 60 min. Subsequently, all samples were
refrigerated for 20 h and were recovered by rinsing with 50 mL sterile Bacto
Peptone water. The collected solution was serially diluted and bacteria
populations were enumerated on selective media, tryptic soy agar, and bril-
liant green agar with nalidixic acid. The results exhibited no significant
reduction in any of the treatments with reductions of less than 1 log
CFU/mL (Chaves et al., 2011).
S. Typhimurium DT104, a multidrug-resistant strain, was used to ana-
lyze its growth on chicken meat under cold stress storage since it can be enu-
merated in the presence of other microorganisms and because it was
previously isolated from chicken (Oscar, 2014). Chicken breasts, thighs,
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and skin were inoculated by spotting the surface with S. Typhimurium

DT104. Subsequently, they were stored at cold storage from 8°C to
16°C for 0–8 days. Results indicated that when samples were inappropri-
ately refrigerated at 12–16°C, S. Typhimurium DT104 proliferated at the
highest level on thighs, followed by the skin and breast meat (Oscar, 2014).
4.4 Other Food Products

The relationship between chicken eggs and S. Enteritidis continues to be a
concern since the initial outbreaks occurred several decades ago (Galiş et al.,
2013; Howard et al., 2012; Ricke, 2003a, 2017). This is due to the ability of
S. Enteritidis to either externally penetrate the egg shell and reach the inner
part of the egg or being deposited internally by transovarian contamination
during formation of the egg after colonization of the reproductive tract
(Galiş et al., 2013; Gantois et al., 2009; Ricke, 2017). Once reaching the
inner part of the egg, it can, depending upon the internal temperature of
the egg, multiply quite rapidly (Galiş et al., 2013; Howard et al., 2012).
To restrain S. Enteritidis growth in eggs has been the focus of developing
methods to rapidly cool eggs before prolonged storage (Galiş et al.,
2013). Theron, Venter, and Lues (2003) reported that a cold shock 4°C
for 4–6 h followed by storage and transport at 25°C was the most effective
in limiting the growth of microbial populations including both Salmonella
and non-Salmonella microorganisms on egg shells and in egg contents.
Clearly the time it takes to reduce temperature to refrigeration level is
important. For example, Chen, Anantheswaran, and Knabel (2002) inocu-
lated internal shell egg contents with S. Enteritidis at a level of 10 cells and
cooled eggs by either rapid cooling from 27°C to 7.2°C in a range of
6–6.5 min depending on the cooling method vs traditional cooling which
required 142 h to reach 7.2°C. All eggs after cooling were stored at 7.2°C
until sampled for S. Enteritidis. For rapidly cooled eggs, S. Enteritidis
growth in the yolk and albumen was inhibited but yolk populations quickly
multiplied (up 107 CFU within 3 days) in the slowly cooled eggs even
though they did not grow in the albumen probably due to the presence
of eggborne antimicrobial defenses as noted by the authors. The preponder-
ance of growth in the yolk supports why transovarian internal contamination
that does not come into contact with the albumen could be particularly
problematic. Gast, Holt, and Guraya (2006) demonstrated that immediate
refrigeration at 7°C also prevented S. Enteritidis already internalized in
the egg on the egg yolk membrane from penetrating the membrane and
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contaminating the yolk while storage at higher temperatures before refrig-

eration led to an invasion of the yolk.
Fresh produce and vegetables continue to be identified with foodborne
pathogens including Salmonella and the issues associated with processing and
control measures have been described extensively elsewhere (Erickson,
2010; Hanning et al., 2009; Lynch et al., 2009) and will not be discussed
in the current review. However, refrigerated juices have come under spe-
cific scrutiny as a source of Salmonella to the point of a federal regulatory
edict to institute treatments that reduce pathogens such as Salmonella by 5
logs in the United States (FDA, 2001; Parrish, Goodrich, & Miller,
2004). The confounding issue is that because juices are a high-acid food
product, the potential for acid adaptation and cross-protection does exist.
Yuk and Schneider (2006) demonstrated this experimentally when they
showed that Salmonella in stored juices exhibited enhanced survival in sim-
ulated gastric juice. When acid-adapted (pH 5, 0.25% anhydrous citric acid)
Salmonella species were stored at various refrigeration temperatures in either
grapefruit or orange concentrate and sampled periodically for survivors,
considerable differences were observed by Parrish et al. (2004). For the
orange concentrate 2.3–4.8 Salmonella log reductions occurred after 50 days,
while the time frame was much shorter for grapefruit concentrate reaching
log reductions of 6.0–6.9 after only 11 days. Given the differences in the two
juice concentrates, it would be of interest to do a detailed study on the
respective concentrations particularly the types and levels of acids. Yuk
and Schneider (2006) also noted differences in survival of Salmonella
according to juice type as well as differences in serovars.
5. CONCLUSIONS
Bacteria can encounter unexpected downshifts of temperature in the
environment that will require them to generate cellular physical and bio-
chemical modifications in response to gene expression regulation. This
includes maintaining cell membrane fluidity, DNA supercoiling modifica-
tions, CSPs, mRNA secondary structure modulation, and other mechanisms
depending on the cold shock level and exposure time. Salmonella can express
physiological and genetic responses to cold stress; they can survive for long
periods of time during cold environment and induce various modifications
including cross-protection to other stressors and virulence factors. In some
case, cold stress caused an enhancement of Salmonella pathogenicity by
increasing adhesion and invasion to epithelial cells, demonstrating exposure
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to cold environments during manufacturing, transporting, and storage could

be a considerable problem for food safety. Whether this needs to be consid-
ered a risk factor is unclear at this time since it is not known how transient
some of the responses are. Other issues such as serovar differences also need
to be examined. Therefore, the mechanisms of Salmonella stress response to
cold will need to be studied more in-depth not only for individual serovars
but across different serovars to achieve better control of Salmonella using cold
temperature in the food industries.
ACKNOWLEDGMENTS
Author T.M.D. was supported by a scholarship from King Saud University, Riyadh, Saudi
Arabia. During his graduate work, he was partially funded by a grant from the Deanship of
Scientific Research, King Saud University (Research Group No. RGP-VPP-020). Author
S.A.K. was initially supported by Basic Science Research Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-
2015R1A6A3A03016811).
REFERENCES
Abee, T., & Wouters, J. A. (1999). Microbial stress response in minimal processing. Interna-
tional Journal of Food Microbiology, 50, 65–91.
Aldsworth, T. G., Sharman, R. L., Dodd, C. E. R., & Stewart, G. S. A. B. (1998).
A competitive microflora increases the resisitance of Salmonella typhimurium to inimical
processes: Evidence for a suicide response. Applied and Environmental Microbiology, 64,
1323–1327.
Alzamora, S., Tapia, M., & Chanes, J. W. (1998). New strategies for minimally processed
foods. The role of multitarget preservation/Nuevas estrategias para los alimentos mı́n-
imamente procesados. La conservación “multiblanco” Food Science and Technology Inter-
national, 4, 353–361.
Andino, A., & Hanning, I. (2015). Salmonella enterica: Survival, colonization, and virulence
differences among serovars. The Scientific World Journal, 2015, 520179. https://doi.org/
10.1155//2015/520179.
Archer, D. L. (1996). Preservation microbiology and safety: Evidence that stress enhances
virulence and triggers adaptive mutations. Trends in Food Science and Technology, 7, 91–95.
Archer, D. L. (2004). Freezing: An underutilized food safety technology? International Journal
of Food Microbiology, 90, 127–138.
Atlung, T., Clausen, E. S., & Hansen, F. G. (1985). Autoregulation of the dnaA gene of
Escherichia coli K12. Molecular and General Genetics, 200, 442–450.
Atlung, T., & Hansen, F. G. (1999). Low-temperature-induced DnaA protein synthesis does
not change initiation mass in Escherichia coli K-12. Journal of Bacteriology, 181, 5557–5562.
Bae, W., Xia, B., Inouye, M., & Severinov, K. (2000). Escherichia coli CspA-family RNA
chaperones are transcription antiterminators. Proceedings of the National Academy of Sciences
of the United States of America, 97, 7784–7789.
Barria, C., Malecki, M., & Arraiano, C. M. (2013). Bacterial adaptation to cold. Microbiology,
159, 2437–2443.
Beales, N. (2004). Adaptation of microorganisms to cold temperatures, weak acid preserva-
tives, low pH, and osmotic stress: A review. Comprehensive Reviews in Food Science and
Food Safety, 3, 1–20.
ARTICLE IN PRESS
Bearson, S. M. D., Bearson, B. L., Lee, I. S., & Kich, J. D. (2013). Polynucleotide phosphor-
ylase (PNPase) is required for Salmonella enterica serovar Typhimurium colonization in
swine. Microbial Pathogenesis, 65, 63–66.
Berry, E. D., & Foegeding, P. M. (1997). Cold temperature adaptation and growth of micro-
organisms. Journal of Food Protection, 60, 1583–1594.
Boor, K. J. (2006). Bacterial stress responses: What doesn’t kill them can make them stronger.
PLoS Biology, 4, e23. https://doi.org/10.1371/journal.pbio.0040023.
Brands, D. A., Inman, A. E., Gerba, C. P., Mare, C. J., Billington, S. J., Saif, L. A., et al.
(2005). Prevalence of Salmonella spp. in oysters in the United States. Applied and Environ-
mental Microbiology, 71, 893–897.
Braun, R. E., O’Day, K., & Wright, A. (1985). Autoregulation of the DNA replication gene
dnaA in E. coli K-12. Cell, 40, 159–169.
Buncic, S., & Sofos, J. (2012). Interventions to control Salmonella contamination during
poultry, cattle and pig slaughter. Food Research International, 45, 641–655.
Cairncross, S., Hunt, C., Boisson, S., Bostoen, K., Curtis, V., Fung, I. C., et al. (2010).
Water, sanitation and hygiene for the prevention of diarrhoea. International Journal of Epi-
demiology, 39, i193–i205.
Cameron, A. D. S., Stoebel, D. M., & Dorman, C. J. (2011). DNA supercoiling is differen-
tially regulated by environmental factors and FIS in Escherichia coli and Salmonella enterica.
Molecular Microbiology, 80, 85–101.
Champoux, J. J. (2001). DNA topoisomerases: Structure, function, and mechanism. Annual
Review of Biochemistry, 70, 369–413.
Chattopadhyay, M. (2006). Mechanism of bacterial adaptation to low temperature. Journal of
Biosciences, 31, 157–165.
Chaves, B., Han, I., Dawson, P., & Northcutt, J. (2011). Survival of artificially inoculated
Escherichia coli and Salmonella Typhimurium on the surface of raw poultry products sub-
jected to crust freezing. Poultry Science, 90, 2874–2878.
Chen, H., Anantheswaran, C., & Knabel, S. (2002). Effect of rapid cooling on the growth and
penetration of Salmonella Enteritidis into egg contents. Journal of Food Safety, 22, 255–271.
Chiok, K. L., Addwebi, T., Guard, J., & Shah, D. H. (2013). Dimethyl adnosine transferase
(KsgA) deficiency in Salmonella enterica serovar Enteritidis confers susceptibility to high
osmolarity and virulence attenuation in chickens. Applied and Environmental Microbiology,
79, 7857–7866.
Clements, M. O., Eriksson, S., Thompson, A., Lucchini, S., Hinton, J. C. D., Normark, S.,
et al. (2002). Polynucleotide phosphorylase is a global regulator of virulence and persis-
tency in Salmonella enterica. Proceedings of the National Academy of Sciences of the United States
of America, 99, 8784–8789.
Cordin, O., Banroques, J., Tanner, N. K., & Linder, P. (2006). The DEAD-box protein
family of RNA helicases. Gene, 367, 17–37.
Craig, J. E., Boyle, D., Francis, K. P., & Gallagher, M. P. (1998). Expression of the cold-
shock gene cspB in Salmonella typhimurium occurs below a threshold temperature.
Microbiology, 144, 697–704.
Crandall, P. G., O’Bryan, C. A., Babu, D., Jarvis, N., Davis, M. L., Buser, M., et al. (2013).
Whole-chain traceability, is it possible to trace your hamburger to a particular steer, a US
perspective. Meat Science, 95, 137–144.
Dadzie, I., Xu, S., Ni, B., Zhang, X., Zhang, H., Sheng, X., et al. (2013). Identification and
characterization of a cis-encoded antisense RNA associated with the replication process
of Salmonella enterica serovar Typhi. PLoS ONE, 8(4), e61308. https://doi.org/10.1371/
journal.pone.0061308.
Dainty, R. H., & Mackey, B. M. (1992). The relationship between the phenotype properties
of bacteria from chill-stored meat and spoilage processes. Journal of Applied Bacteriology,
73, 103S–114S [Symposium Supplement].
ARTICLE IN PRESS
Dammel, C. S., & Noller, H. F. (1995). Suppresion of a cold-sensitive mutation in 16S

rRNA by overexpression of a novel ribosome-binding factor, RbfA. Genes and Develop-
ment, 9, 626–637.
Davies, R., Dalziel, R., Gibbens, J., Wilesmith, J., Ryan, J., Evans, S., et al. (2004). National
survey for Salmonella in pigs, cattle and sheep at slaughter in Great Britain (1999–2000).
Journal of Applied Microbiology, 96, 750–760.
Dawoud, T. M., Davis, M. L., Park, S. H., Kim, S. A., Kwon, Y. M., Jarvis, N., et al. (2017).
Salmonella thermal resistance—Molecular responses. Frontiers in Veterinary Sciences, 4, 93.
https://doi.org/10.33889/fvets.2017.00093.
de Freitas Neto, O., Penha Filho, R., Barrow, P., & Berchieri Junior, A. (2010). Sources of
human non-typhoid salmonellosis: A review. Revista Brasileira de Ci^encia Avı´cola, 12,
01–11.
Di Pasqua, R., Mauriello, G., Mamone, G., & Erclolini, D. (2013). Expression of DnaK,
HtpG, GroEL, and Tf chaperones and the corresponding encoding genes during growth
of Salmonella Thompson in presence of thymol alone or in combination with salt and cold
stress. Food Research International, 52, 153–159.
Dinçer, A. H., & Baysal, T. (2004). Decontamination techniques of pathogen bacteria in
meat and poultry. Critical Reviews in Microbiology, 30, 197–204.
Dominguez, S. A., & Schaffner, D. W. (2009). Survival of Salmonella in processed chicken
products during frozen storage. Journal of Food Protection, 72, 2088–2092.
Dorman, C. J. (1991). DNA supercoiling and environmental regulation of gene expression in
pathogenic bacteria. Infection and Immunity, 59, 745–749.
Dorman, C. J. (2006). DNA supercoiling and bacterial gene expression. Scientific Progress, 89,
151–166.
Dykes, G., & Moorhead, S. (2001). Survival of three Salmonella serotypes on beef trimmings
during simulated commercial freezing and frozen storage. Journal of Food Safety, 21,
87–96.
Erickson, M. C. (2010). Microbial risks associated with cabbage, carrots, celery, onions, and
deli salads made with these produce items. Comprehensive Reviews in Food Science and Food
Safety, 9, 602–619.
Eriksson, S., Hurme, R., & Rhen, M. (2002). Low temperature sensors in bacteria. Philosoph-
ical Transactions of the Royal Society of London, Series B, 357, 887–893.
Ermolenko, D., & Makhatadze, G. (2002). Bacterial cold-shock proteins. Cellular and Molec-
ular Life Sciences, 59, 1902–1913.
Fang, L., Jiang, W., Bae, W., & Inouye, M. (1997). Promoter-independent cold-shock
induction of cspA and its derepression at 37°C by mRNA stabilization. Molecular Micro-
biology, 23, 355–364.
Finstad, S., O’Bryan, C. A., Marcy, J. A., Crandall, P. G., & Ricke, S. C. (2012). Salmonella
and broiler processing in the United States: Relationship to foodborne salmonellosis.
Food Research International, 45, 789–794.
Foley, S. L., Johnson, T. J., Ricke, S. C., Nayak, R., & Danzeisen, J. (2013). Salmonella path-
ogenicity and host adaptation in chicken-associated serovars. Microbiology and Molecular
Biology Reviews, 77, 582–607.
Foley, S., Nayak, R., Hanning, I. B., Johnson, T. J., Han, J., & Ricke, S. C. (2011). Pop-
ulation dynamics of Salmonella enterica serotypes in commercial egg and poultry produc-
tion. Applied and Environmental Microbiology, 77, 4273–4279.
Food and Drug Administration. (2001). 21 CFR part 120 hazard analysis and critical control
point [HAACP]; procedures for the safe and sanitary processing and inporting of juice;
final rule. Federal Register, 66, 6137–6202.
Foster, J. W. (1999). When protons attack: Microbial strategies of acid adaptation. Current
Opinion in Microbiology, 2, 170–174.
ARTICLE IN PRESS
Galiş, A. M., Marcq, C., Marlier, D., Portetelle, D., Van, I., Beckers, Y., et al. (2013). Con-
trol of Salmonella contamination of shell eggs—Preharvest and postharvest methods:
A review. Comprehensive Reviews in Food Science and Food Safety, 12, 155–182.
Gantois, I., Ducatelle, R., Pasmans, F., Haesebrouck, F., Gast, R., & Humphrey, T. J.
(2009). Mechanisms of egg contamination by Salmonella Enteritidis. FEMS Microbiology
Reviews, 33, 718–738.
Gast, R. K., Holt, P. S., & Guraya, R. (2006). Effect of refrigeration on in vitro penetration of
Salmonella Enteritidis through the egg yolk membrane. Journal of Food Protection, 69,
1426–1429.
Giuliodori, A. M., Di Pietro, F., Marzi, S., Masquda, B., Wagner, R., Romby, P., et al.
(2010). The cspA mRNA is a thermosensor that modulates translation of the cold-shock
protein CspA. Molecular Cell, 37, 21–33.
Golovlev, E. (2003). Bacterial cold shock response at the level of DNA transcription, trans-
lation, and chromosome dynamics. Microbiology, 72, 1–7.
Gomez-Gomez, J. M., Manfredi, C., Alonso, J. C., & Blazquez, J. (2007). A novel role for
RecA under non-stress promotion of swarming motility in Escherichia coli K-12. BMC
Biology, 5, 14.
González-Gil, F., Le Bolloch, A., Pendleton, S., Zhang, N., Wallis, A., & Hanning, I. (2012).
Expression of hilA in response to mild acid stress in Salmonella enterica is serovar and strain
dependent. Journal of Food Science, 77, M292–M297.
Gualerzi, C. O., Giuliodori, A. M., & Pon, C. L. (2003). Transcriptional and post-
transcriptional control of cold-shock genes. Journal of Molecular Biology, 331, 527–539.
Guillard, V., Mauricio-Iglesias, M., & Gontard, N. (2010). Effect of novel food processing
methods on packaging: Structure, composition, and migration properties. Critical Reviews
in Food Science and Nutrition, 50, 969–988.
Gyles, C. L. (2008). Antimicrobial resistance in selected bacteria from poultry. Animal Health
Research Reviews, 9, 149–158.
Haddad, N., Burns, C. M., Bolla, J. M., Prevost, H., Federighi, M., Drider, D., et al. (2009).
Long-term survival of Campylobacter jejuni at low temperatures is dependent on polynu-
cleotide phosphorylase activity. Applied and Environmental Microbiology, 75, 7310–7318.
Han, M.-J., & Lee, S. Y. (2006). The Escherichia coli proteome: Past, present, and future pros-
pects. Microbiology and Molecular Biology Reviews, 70, 362–439.
Hanning, I. B., Nutt, J., & Ricke, S. C. (2009). Salmonellosis outbreaks in the United States
due to fresh produce: Sources and potential intervention measures. Foodborne Pathogens
and Disease, 6, 635–648.
Hapfelmeier, S., Stecher, B., Barthel, M., Kremer, M., M€ uller, A. J., Heikenwalder, M., et al.
(2005). The Salmonella pathogenicity island (SPI)-2 and SPI-1 type III secretion systems
allow Salmonella serovar typhimurium to trigger colitis via MyD88-dependent and
MyD88-independent mechanisms. The Journal of Immunology, 174, 1675–1685.
Hatfield, G. W., & Benham, C. J. (2002). DNA topology-mediated control of global expres-
sion in Escherichia coli. Annual Reviews in Genetics, 36, 175–203.
Heaton, J., & Jones, K. (2008). Microbial contamination of fruit and vegetables and the
behaviour of enteropathogens in the phyllosphere: A review. Journal of Applied Microbi-
ology, 104, 613–626.
Hebraud, M., & Potier, P. (1999). Cold shock response and low temperature adaptation in
psychrotrophic bacteria. Journal of Molecular Microbiology and Biotechnology, 1, 211–219.
Heinitz, M. L., Ruble, R. D., Wagner, D. E., & Tatini, S. R. (2000). Incidence of Salmonella
in fish and seafood. Journal of Food Protection, 63, 579–592.
Heithoff, D. M., Shimp, W. R., House, J. K., Xie, Y., Weimer, B. C., Sinsheimer, R. L.,
et al. (2012). Intraspecies variation in the emergence of hyperinfectious bacterial strains in
nature. PLoS Pathogens, 8, e1002647.
ARTICLE IN PRESS
Horne, S. M., Kottom, T. J., Nolan, L. K., & Young, K. D. (1997). Decreased intracellular
survival of an fkpA mutant of Salmonella typhimurium Copenhagen. Infection and Immunity,
65, 806–810.
Horton, A. J., Hak, K. M., Steffan, R. J., Foster, J. W., & Bej, A. K. (2000). Adaptive
response to cold temperatures and characterization of cspA in Salmonella typhimurium
LT2. Antonie van Leeuwenhoek, 77, 13–20.
Howard, Z. R., O’Bryan, C. A., Crandall, P. G., & Ricke, S. C. (2012). Salmonella
Enteritidis in shell eggs: Current issues and prospects for control. Food Research Interna-
tional, 45, 755–764.
Howe, J. G., & Hershey, J. W. B. (1984). The rate of evolutionary divergence of intiation
factors IF2 and IF3 in various bacterial species determined quantitatively by immuno-
blotting. Archives of Microbiology, 140, 187–192.
Hu, J., McCormick, R. J., Means, W. J., & Zhu, M.-J. (2014). Polynucleotide phosphorylase
is required for Escherichia coli O157:H7 growth above refrigerated temperature. Foodborne
Pathogens and Disease, 11, 177–185.
Jarvis, N. A., O’Bryan, C. A., Dawoud, T. M., Park, S. H., Kwon, Y. M., Crandall, P. G.,
et al. (2016). An overview of Salmonella thermal destruction during food processing and
preparation. Food Control, 68, 280–290.
Jeffreys, A. G., Hak, K. M., Steffan, R. J., Foster, J. W., & Bej, A. K. (1998). Growth, survival
and characterization of cspA in Salmonella enteritidis following cold shock. Current Micro-
biology, 36, 29–35.
Jennings, E., Thurston, T. L., & Holden, D. W. (2017). Salmonella SPI-2 type III secretion
system effectors: Molecular mechanisms and physiological consequences. Cell Host &
Microbe, 22, 217–231.
Jones, P. G., & Inouye, M. (1994). The cold shock response—A hot topic. Molecular
Mirobiology, 11, 811–818.
Jones, P. G., Krah, R., Tafuri, S. R., & Wolffe, A. P. (1992). DNA gyrase CS7.4, and the
cold shock response in Escherichia coli. Journal of Bacteriology, 174, 5798–5802.
Jones, P. G., VanBogelen, R. A., & Neidhardt, F. C. (1987). Induction of
proteins in response to low temperature in Escherichia coli. Journal of Bacteriology, 169,
2092–2095.
Kaberdin, V. R., & Bl€asi, U. (2013). Bacterial helicases in post-transcriptional control.
Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 1829, 878–883.
Kaczanowska, M., & Ryden-Aulin, M. (2007). Ribosome biogenesis and the translation pro-
cess in Escherichia coli. Microbiology and Molecular Biology Reviews, 71, 477–494.
Kaguni, J. M. (2006). DnaA: Controlling the initiation of bacterial DNA replication and
more. Annual Review of Microbiology, 60, 351–371.
Kandror, O., & Goldberg, A. L. (1997). Trigger factor is induced upon cold shock and
enhances viability of Escherichia coli at low temperatures. Proceedings of the National Acad-
emy of Sciences of the United States of America, 94, 4978–4981.
Khemici, V., & Linder, P. (2016). RNA helicases in bacteria. Current Opinion in Microbiology,
30, 58–66.
Kim, B. H., Bang, I. S., Lee, S. Y., Hong, S. K., Bang, S. H., Lee, I. S., et al. (2001). Expres-
sion of cspH, encoding the cold shock protein in Salmonella enterica serovar Typhimurium
UK-1. Journal of Bacteriology, 183, 5580–5588.
Kim, B. H., Kim, H. G., Bae, G. I., Bang, I. S., Bang, S. H., Choi, J. H., et al. (2004). Expres-
sion of cspH upon nutrient up-shift in Salmonella enterica serovar Typhimurium. Archives in
Kim, B. H., Kim, S., Kim, H. G., Lee, J., Lee, I. S., & Park, Y. K. (2005). The formation of
cyclopropane fatty acids in Salmonella enterica serovar Typhimurium. Microbiology, 151,
209–218.
ARTICLE IN PRESS
Kwon, Y. M., Park, S. Y., Birkhold, S. G., & Ricke, S. C. (2000). Induction of resistance of
Salmonella typhimurium to environmental stresses by exposure to short-chain fatty acids.
Journal of Food Science, 65, 1037–1040.
Kwon, Y. M., & Ricke, S. C. (1998). Induction of acid resistance of Salmonella typhimurium
by exposure to short-chain fatty acids. Applied and Environmental Microbiology, 64,
3458–3463.
La Teana, A., Brandi, A., Falconi, M., Spurio, R., Pon, C. L., & Gualerxi, C. O. (1991).
Identification of a cold shock transcriptional enhancer of the Escherichia coli gene
encoding nucleoid protein H-NS. Proceedings of the National Academy of Sciences of the
United States of America, 88, 10907–10911.
Laursen, B. S., Mortensen, K. K., Sperling-Petersen, H. U., & Hoffman, D. W. (2003).
A conserved structural motif at the N terminus of bacterial translation initiation factor
IF2. Journal of Biological Chemistry, 278, 16320–16328.
Laursen, B. S., Sørensen, H. P., Mortensen, K. K., & Sperling-Petersen, H. U. (2005). Ini-
tiation of protein synthesis in bacteria. Microbiology and Molecular Biology Reviews, 69,
101–123.
Lee, P. S., & Lee, K. H. (2003). Escherichia coli—A model system that benefits from and con-
tributes to the evolution of proteomics. Biotechnology and Bioengineering, 84, 801–814.
Li, Y., Meng, Q.-F., Wang, W. L., & Sun, X.-Y. (2012). Differential expression of ATP-
dependent RNA helicase gene in viable but nonculturable Salmonella pullorum. African
Journal of Biotechnology, 11, 2625–2630.
López-Garcı́a, P. (1999). DNA supercoiling and temperature adaptation: A clue to early
diversification of life? Journal of Molecular Evolution, 49, 439–452.
Loretz, M., Stephan, R., & Zweifel, C. (2010). Antimicrobial activity of decontamination
treatments for poultry carcasses: A literature survey. Food Control, 21, 791–804.
Los, D., Horvath, I., Vigh, L., & Murata, N. (1993). The temperature-dependent expression
of the desaturase gene desA in Synechocystis PCC6803. FEBS Letters, 318, 57–60.
Los, D. A., & Murata, N. (2004). Membrane fluidity and its roles in the perception
of environmental signals. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1666,
142–157.
Lynch, M., Tauxe, R., & Hedberg, C. (2009). The growing burden of foodborne outbreaks
due to contaminated fresh produce: Risks and opportunities. Epidemiology and Infection,
137, 307–315.
Mah, T.-F., Kuznedelov, K., Mushegian, A., Severinov, K., & Greenblatt, J. (2000). The α
subunit of E. coli RNA polymerase activates RNA binding by NusA. Genes and Devel-
opment, 14, 2664–2675.
Mansilla, M. C., Cybulski, L. E., Albanesi, D., & de Mendoza, D. (2004). Control
of membrane lipid fluidity by molecular thermosensors. Journal of Bacteriology, 186,
6681–6688.
Marr, A. G., & Ingraham, J. L. (1962). Effect of temperature on the composition of fatty acids
in Escherichia coli. Journal of Bacteriology, 84, 1260–1267.
Martinez-Urtaza, J., Peiteado, J., Lozano-León, A., & Garcia-Martin, O. (2004). Detection
of Salmonella Senftenberg associated with high saline environments in mussel processing
facilities. Journal of Food Protection, 67, 256–263.
Mathy, N., Jarrige, A.-C., Robert-Le Meur, M., & Portier, C. (2001). Increased expression
of Escherichia coli polynucleotide phosphorylase at low temperatures is linked to a decrease
in the efficiency of autocontrol. Journal of Bacteriology, 183, 3848–3854.
Mayola, A., Irazoki, O., Martinez, I. A., Petrov, D., Menolascina, F., Stocker, R., et al.
(2014). RecA protein plays a role in the chemotatic response and chemoreceptor clus-
tering of Salmonella enterica. PLoS ONE, 9(8), e105578. https://doi.org/10.1371/journal.
pone.0105578.
ARTICLE IN PRESS
McClinden, T., Sargeant, J. M., Thomas, M. K., Papadopoulos, A., & Fazil, A. (2014).
Association between component costs, study methodologies, and foodborne illness-
related factors with the cost of nontyphoidal Salmonella illness. Foodborne Pathogens and
Disease, 11, 718–726.
McDonald, K., & Sun, D.-W. (2000). Vacuum cooling technology for the food processing
industry: A review. Journal of Food Engineering, 45, 55–65.
McMeechan, A., Roberts, M., Cogan, T. A., Jørgensen, F., Stevenson, A., Lewis, C., et al.
(2007). Role of the alternative sigma factors σE and σS in survival of Salmonella enterica
serovar Typhimurium during starvation, refrigeration and osmotic shock. Microbiology,
153, 263–269.
Medina-Ruiz, L., Campoy, S., Latasa, C., Cardenas, P., Alonso, J. C., & Barbe, J. (2010).
Overexpression of the recA gene decreases oral but not intraperitoneal fitness of Salmo-
nella enterica. Infection and Immunity, 78, 3217–3225.
Messer, W., & Weigel, C. (1997). DnaA initiator—Also a transcription factor. Molecular
Mirkin, S. M. (2001). DNA topology: Fundamentals, encyclopedia of life sciences (ELS) (pp. 1–11).
Chichester, West Sussex, UK: John Wiley & Sons, Ltd.
Mizushima, T., Kataoka, K., Ogata, Y., Inoue, R. I., & Sekimizu, K. (1997). Increase in
negative supercoiling of plasmid DNA in Escherichia coli exposed to cold shock. Molecular
Morgan, H. P., Wear, M. A., McNae, I., Gallagher, M. P., & Walkinshaw, M. D. (2009).
Crystallization and X-ray structure of cold—shock protein E from Salmonella typ-
himurium. Acta Crystallographica. Section F, Structural Biology and Crystallization Communi-
cations, F65, 1240–1245.
M€uller, K., Aabo, S., Birk, T., Mordhorst, H., Bjarnadóttir, B., & Agersø, Y. (2012). Survival
and growth of epidemically successful and nonsuccessful Salmonella enterica clones after
freezing and dehydration. Journal of Food Protection, 75, 456–464.
Neuhaus, K., Francis, K. P., Rapposch, S., G€ org, A., & Scherer, S. (1999). Pathogenic
Yersinia species carry a novel, cold-inducible major cold shock protein tandem gene
duplication producing both bicistronic and monocistronic mRNA. Journal of Bacteriology,
181, 6449–6455.
Neuhaus, K., Rapposch, S., Francis, K. P., & Scherer, S. (2000). Restart of exponential
growth of cold-shocked Yersinia enterocolitica occurs after down-regulation of cspA1/
A2 mRNA. Journal of Bacteriology, 182, 3285–3288.
Nishi, K., & Schnier, J. (1986). A temperature-sensitive mutant in the gene rplX for ribosomal
protein L24 and its suppression by spontaneous mutations in a 23S rRNA gene of
Escherichia coli. The EMBO Journal, 5, 1373–1376.
Nishi, K., & Schnier, J. (1988). The phenotypic suppression of a mutation in the gene rplX for
ribosomal protein L24 by mutations affecting the lon gene product for protease LA in
Escherichia coli K12. Molecular and General Genetics MGG, 212, 177–181.
O’Ryan, M., Prado, V., & Pickering, L. K. (2005). In A millennium update on pediatric diarrheal
illness in the developing world. Seminars in pediatric infectious diseases (pp. 125–136). Elsevier.
Oscar, T. P. (2014). General regression neural network model for behavior of Salmonella on
chicken meat during cold storage. Journal of Food Science, 79, M978–M987.
Panoff, J.-M., Thammavongs, B., Gueguen, M., & Boutibonnes, P. (1998). Cold stress
responses in mesophilic bacteria. Cryobiology, 36, 75–83.
Park, S. Y., Woodward, C. L., Kubena, L. F., Nisbet, D. J., Birkhold, S. G., & Ricke, S. C.
(2008). Environmental dissemination of foodborne Salmonella in preharvest poultry pro-
duction: Reservoirs, critical factors and research strategies. Critical Reviews in Environmen-
tal Science and Technology, 38, 73–111.
Parrish, M. E., Goodrich, R., & Miller, W. (2004). Fate of salmonellae in orange and grape-
fruit concentrate during cold storage. Journal of Food Protection, 67, 2671–2674.
ARTICLE IN PRESS
Pavlov, M. Y., Zorzet, A., Andersson, D. I., & Ehrenberg, M. (2011). Activation of initiation
facotr 2 by ligands and mutations for rapid docking of ribosomal subunits. The EMBO
Journal, 30, 289–301.
Peil, L., Virum€ae, K., & Remme, J. (2008). Ribosome assembly in Escherichia coli strains lac-
king the RNA helicase DeaD/CsdA or DbpA. FEBS Journal, 275, 3772–3782.
Phadtare, S. (2004). Recent developments in bacterial cold-shock response. Current Issues in
Molecular Biology, 6, 125–136.
Phadtare, S., & Severinov, K. (2010). RNA remodeling and gene regulation by cold shock
proteins. RNA Biology, 7, 788–795.
Phillips, L., Humphrey, T., & Lappin-Scott, H. (1998). Chilling invokes different
morphologies in two Salmonella enteritidis PT4 strains. Journal of Applied Microbiology,
84, 820–826.
Pires, S. M., Viera, A. R., Hald, T., & Cole, D. (2014). Source attribution of human salmo-
nellosis: An overview of methods and estimates. Foodborne Pathogens and Disease, 11,
667–676.
Pittman, C. I., Pendleton, S., Bisga, B., O’Bryan, C. O., Belk, K. E., Goodridge, L., et al.
(2011). Activity of citrus essential oils against Escherichia coli O157:H7 and Salmonella spp.
and effects on beef subprimal cuts under refrigeration. Journal of Food Science, 76,
M433–M438.
Podewils, L. J., Mintz, E. D., Nataro, J. P., & Parashar, U. D. (2004). Acute, infectious diarrhea
among children in developing countries. In Seminars in pediatric infectious diseases (pp. 155–168).
WB Saunders.
Polissi, A., De Laurentis, W., Zangrossi, S., Briani, F., Longhi, V., Pesole, G., et al. (2003).
Changes in Escherichia coli transcriptome during acclimatization at low temperature.
Research in Microbiology, 154, 573–580.
Prakash, J. S., Sinetova, M., Zorina, A., Kupriyanova, E., Suzuki, I., Murata, N., et al. (2009).
DNA supercoiling regulates the stress-inducible expression of genes in the cyanobacte-
rium Synechocystis. Molecular BioSystems, 5, 1904–1912.
Qing, G., Xia, B., & Inouye, M. (2003). Enhancement of translation initiation by A/T-rich
sequences downstream of the initiation codon in Escherichia coli. Journal of Molecular Micro-
biology and Biotechnology, 6, 133–144.
Rajashekara, G., Haverly, E., Halvorson, D., Ferris, K., Lauer, D., & Nagaraja, K. (2000).
Multidrug-resistant Salmonella typhimurium DT104 in poultry. Journal of Food Protection,
63, 155–161.
Ramos, J. L., Gallegos, M.-T., Marques, S., Ramos-González, M.-I., Espinosa-Urgel, M., &
Segura, A. (2001). Responses of Gram-negative bacteria to certain environmental
stressors. Current Opinion in Microbiology, 4, 166–171.
Rangel, D. E. (2011). Stress induced cross-protection against environmental challenges on
prokaryotic and eukaryotic microbes. World Journal of Microbiology and Biotechnology,
27, 1281–1296.
Ricke, S. C. (2003a). The gastrointestinal tract ecology of Salmonella Enteritidis colonization
in molting hens. Poultry Science, 82, 1003–1007.
Ricke, S. C. (2003b). Perspectives on the use of organic acids and short chain fatty acids as
antimicrobials. Poultry Science, 82, 632–639.
Ricke, S. C. (2017). Insights and challenges of Salmonella infections in laying hens. Current
Opinion in Food Science, 18, 43–49.
Ricke, S. C., Kundinger, M. M., Miller, D. R., & Keeton, J. T. (2005). Alternatives to anti-
biotics: Chemical and physical antimicrobial interventions and foodborne pathogen
response. Poultry Science, 84, 667–675.
Rowley, G., Spector, M., Kormanec, J., & Roberts, M. (2006). Pushing the envelope:
Extracytoplasmic stress responses in bacterial pathogens. Nature Reviews Microbiology, 4,
383–394.
ARTICLE IN PRESS
Russell, N. J. (1990). Cold adaptation of microorganisms. Philosophical Transactions of the Royal

Society of London. Series B, Biological Sciences, 326, 79–95.
Russell, N. J. (2002). Bacterial membranes: The effects of chill storage and food processing.
An overview. International Journal of Food Microbiology, 79, 27–34.
Santosham, M., Chandran, A., Fitzwater, S., Fischer-Walker, C., Baqui, A. H., & Black, R.
(2010). Progress and barriers for the control of diarrhoeal disease. The Lancet, 376, 63–67.
Scallan, E., Hoekstra, R. M., Angulo, F. J., Tauxe, R. V., Widdowson, M.-A., Roy, S. L.,
et al. (2011). Foodborne illness acquired in the United States—Major pathogens. Emerg-
ing Infectious Diseases, 17, 7–15.
Scharff, R. L. (2012). Economic burden from health losses due to foodborne illness in the
United States. Journal of Food Protection, 75, 123–131.
Schmidt, W.-P., & Cairncross, S. (2009). Household water treatment in poor populations: Is
there enough evidence for scaling up now? Environmental Science & Technology, 43,
986–992.
Shah, D. H. (2014). RNA sequencing reveals differences between the global transcriptomes
of Salmonella enterica serovar Enteritidis strains with high and low pathogenicities. Applied
and Environmental Microbiology, 80, 896–906.
Shah, D. H., Casavant, C., Hawley, Q., Addwebi, T., Call, D. R., & Guard, J. (2012). Sal-
monella Enteritidis strains from poultry exhibit different responses to acid stress, oxidative
stress, and survival in the egg albumen. Foodborne Pathogens and Disease, 9, 258–264.
Shah, J., Desai, P. T., Chen, D., Stevens, J. R., & Weimer, B. C. (2013). Preadaptation to
cold stress in Salmonella enterica serovar Typhimurium increases survival during subse-
quent acid stress exposure. Applied and Environmental Microbiology, 79, 7281–7289.
Shah, J., Desai, P. T., & Weimer, B. C. (2014). Genetic mechanisms underlying the path-
ogenicity of cold-stressed Salmonella enterica serovar Typhimurium in cultured intestinal
epithelial cells. Applied and Environmental Microbiology, 80, 6943–6953.
Shajani, Z., Sykes, M. T., & Williamson, J. R. (2011). Assembly of bacterial ribosomes.
Annual Review of Biochemistry, 80, 501–526.
Shapiro, R. S., & Cowen, L. E. (2012). Thermal control of microbial development and vir-
ulence: Molecular mechanisms of microbial temperature sensing. MBio, 3, e00238-
00212.
Shivaji, S., & Prakash, J. S. S. (2010). How do bacteria sense and respond to low temperature?
Archives of Microbiology, 192, 85–95.
Sinensky, M. (1974). Homeoviscous adaptation—A homeostatic process that regulates the
viscosity of membrane lipids in Escherichia coli. Proceedings of the National Academy of Sciences
of the United States of America, 71, 522–525.
Singh, R. D., Sarin, S., & Tandon, C. D. (1997). Combat between host and microbes: The
role of stress proteins. Medical Science Research, 25, 573–575.
Skovgaard, O., & Hansen, F. G. (1987). Comparison of dnaA nucleotide sequences of
Escherichia coli, Salmonella typhimurium, and Serratia marscens. Journal of Bacteriology, 169,
3976–3981.
Smadi, H., Sargeant, J. M., Shannon, H. S., & Raina, P. (2012). Growth and inactivation of
Salmonella at low refirgerated storage temperatures and thermal inactivation on raw
chicken meat and laboratory media: Mixed effect meta-analysis. Journal of Epidemiology
and Global Health, 2, 165–179.
Sorrells, K., Speck, M., & Warren, J. (1970). Pathogenicity of Salmonella gallinarum after met-
abolic injury by freezing. Applied Microbiology, 19, 39–43.
Spector, M. P. (1998). The starvation-stress response (SSR) of Salmonella. Advances in Micro-
bial Physiology, 40, 233–279.
Stella, S., Falconi, M., Lammi, M., Gualerzi, C. O., & Pon, C. L. (2006). Environmental
control of the in vivo oligomerization of nucleoid protein H-NS. Journal of Molecular Biol-
ogy, 355, 169–174.
ARTICLE IN PRESS
Terekhova, K., Gunn, K. H., Marko, J. F., & Mondragón, A. (2012). Bacterial topoisomerase
I and topoisomerase III relax supercoiled DNA via distinct pathways. Nucleic Acids
Research, 40, 10432–10440.
Theron, H., Venter, P., & Lues, J. F. R. (2003). Bacterial growth on chicken eggs in various
storage environments. Food Research International, 16, 969–975.
Thieringer, H. A., Jones, P. G., & Inouye, M. (1998). Cold shock and adaptation. BioEssays,
20, 49–57.
Travers, A., & Muskhelishvili, G. (2005). DNA supercoiling-A global transcriptional regu-
lator for enterobacterial growth? Nature Reviews Microbiology, 3, 157–169.
Tsai, C.-L., Burkinshaw, B. J., Strynadka, N. C., & Tainer, J. A. (2015). The Salmonella type
III secretion system virulence effector forms a new hexameric chaperone assembly for
export of effector/chaperone complexes. Journal of Bacteriology, 197, 672–675.
United States Department of Agriculture - Cold Storage. (2018). National Agriculture Statistics
Service. Released February 22, 2018. www.nass.usda.gov//Cold_Storage/index.php.
Accessed 26.02.18.
United States Department of Agriculture Food Safety and Inspection Service. (2013). How
temperatures affect food. Available at: https://www.fsis.usda.gov/wps/portal/fsis/topics/
food-safety-education/get-answers/food-safety-fact-sheets/safe-food-handling/how-
temperatures-affect-food/ct_index.
Van Immerseel, F., Eeckhaut, V., Boyen, F., Pasmans, F., Hasebrouck, F., & Ducatelle, R.
(2008). Mutations influencing expression of the Salmonella enterica srovar Enteritidis path-
ogenicity island I key regulator hilA. Antonie van Leeuwenhoek, 94, 455–461.
Vigh, L., Los, D. A., Horvath, I., & Murata, N. (1993). The primary signal in the biological
perception of temperature: Pd-catalyzed hydrogenation of membrane lipids stimulated
by expression of the desA gene in Synechocystis PCC6803. Proceedings of the National Acad-
emy of Sciences of the United States of America, 90, 9090–9094.
Waterman, S. R., & Small, P. (1998). Acid-sensitive enteric pathogens are protected from
killing under extremely acidic conditions of pH 2.5 when they are inoculated onto cer-
tain solid food sources. Applied and Environmental Microbiology, 64, 3882–3886.
Weber, M. H., & Marahiel, M. A. (2003). Bacterial cold shock responses. Science Progress, 86,
9–75.
Wegrzyn, G., & Wegrzyn, A. (2002). Stress responses and replication of plasmids in bacterial
cells. Microbial Cell Factories, 1, 2.
Węgrzyn, A., Wrobel, B., & Węgrzyn, G. (1999). Altered biological properties of cell mem-
branes in Escherichia coli dnaA and seqA mutants. Molecular and General Genetics MGG, 261,
762–769.
White-Ziegler, C. A., Um, S., Perez, N. M., Berns, A. L., Malhowski, A. J., & Young, S.
(2008). Low temperature (23°C) increases expression of biofilm-, cold-shock- and
RpoS-dependent genes in Escherichia coli K-12. Microbiology, 154, 148–166.
Wilson, J., Schurr, M., LeBlanc, C., Ramamurthy, R., Buchanan, K., & Nickerson, C.
(2002). Mechanisms of bacterial pathogenicity. Postgraduate Medical Journal, 78, 216–224.
Wollenweber, H.-W., Schlecht, S., Luderritz, O., & Riftschel, E. T. (1983). Fatty acid in
lipopolysaccharides of Salmonella species grown at low temperature. Identification and
position. European Journal of Biochemistry, 130, 167–171.
Wouters, J. A., Sanders, J.-W., Kok, J., de Vos, W. M., Kuipers, O. P., & Abee, T. (1998).
Clustered organization and transcriptional analysis of a family of five csp genes of
Lactococcus lactis MGl363. Microbiology, 144, 2885–2893.
Xu, H., Lee, H., & Ahn, J. (2008). Cross-protective effect of acid-adapted Salmonella enterica
on resistance to lethal acid and cold stress conditions. Letters in Applied Microbiology, 47,
290–297.
Yamanaka, K., Fang, L., & Inouye, M. (1998). The CspA family in Escherichia coli multiple
gene duplication for stress adaptation. Molecular Microbiology, 27, 247–255.
ARTICLE IN PRESS
Yang, L., Zhou, D., Liu, X., Han, H., Zhan, L., Guo, Z., et al. (2009). Cold-induced gene
expression profiles of Vibrio parahaemolyticus: A time-course analysis. FEMS Microbiology
Letters, 291, 50–58.
Ygberg, S. E., Clements, M. O., Rytk€ onen, A., Thompson, A., Holden, D. W.,
Hinton, J. C. D., et al. (2006). Polynucleotide phosphorylase negatively controls spv gene
expression in Salmonella enterica. Infection and Immunity, 74, 1243–1254.
Yuk, H. G., & Schneider, K. R. (2006). Adaptation of Salmonella spp. in juice stored under
refrigerated and room temperature enhances acid resisitance to simulated gastric fluid.
Food Microbiology, 23, 694–700.
Zhang-Akiyama, Q.-M., Morinaga, H., Kikuchi, M., Yonekura, S.-I., Sugiyama, H.,
Yamamoto, K., et al. (2009). KsgA, a 16S rRNA adenine methyltransferase, has a novel
DNA glycosylase/AP lyase activity to prevent mutations in Escherichia coli. Nucleic Acids
Research, 37, 2116–2125.

Salmonella Cold Stress Response - Mechanisms and Occurrence in Foods

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ARTICLE IN PRESS

Salmonella Cold Stress Response:

2 Steven C. Ricke et al.

Salmonella Cold Stress Response 3

4 Steven C. Ricke et al.

investigating general mechanisms associated with bacterial cold stress

2. MOLECULAR MECHANISMS TO COUNTER

2.2 Cold Stress: Physiological Responses

Salmonella Cold Stress Response 5

represent a major physiological challenge to the organism. This exposure

6 Steven C. Ricke et al.

2.3 Cold Shock Response: Molecular Profiles

Salmonella Cold Stress Response 7

2.4 Cell Membrane Modification

8 Steven C. Ricke et al.

lipid A component of lipopolysaccharide in S. Typhimurium or S. Minne-

2.5 DNA Supercoiling Modification

Salmonella Cold Stress Response 9

DNA topoisomerases are the enzymes which function in all DNA-

2.6 CIP Synthesis

10 Steven C. Ricke et al.

2.6.1 Cold Shock Proteins

Salmonella Cold Stress Response 11

previously been demonstrated to be involved in the negative DNA super-

12 Steven C. Ricke et al.

substantial decrease in temperature for induction of the S. Typhimurium

Salmonella Cold Stress Response 13

14 Steven C. Ricke et al.

Salmonella Cold Stress Response 15

2.6.6 Trigger Factor

16 Steven C. Ricke et al.

Salmonella Cold Stress Response 17

2.6.11 Initiation Factors (IFs)

18 Steven C. Ricke et al.

3. SALMONELLA–COLD SHOCK INTERACTION WITH

Salmonella Cold Stress Response 19

The development of cross-protection in Salmonella is known to occur in

3.2 Interaction With Virulence Responses

20 Steven C. Ricke et al.

They evaluated the pathogenicity of uninjured and frozen sublethally

Salmonella Cold Stress Response 21

4. SALMONELLA RESPONSES TO COLD TEMPERATURES

22 Steven C. Ricke et al.

such as ultrasound, high hydrostatic pressure, or pulsed electric field are

Salmonella Cold Stress Response 23

exhibit any significant reductions, whereas strain E expressed significant

24 Steven C. Ricke et al.

4.2 Beef Products

Salmonella Cold Stress Response 25

did not observe a difference in minimum inhibitory concentration of essential

4.3 Chicken Meat Products

26 Steven C. Ricke et al.

and skin were inoculated by spotting the surface with S. Typhimurium

4.4 Other Food Products

Salmonella Cold Stress Response 27

contaminating the yolk while storage at higher temperatures before refrig-

28 Steven C. Ricke et al.

to cold environments during manufacturing, transporting, and storage could

Salmonella Cold Stress Response 29

30 Steven C. Ricke et al.

Dammel, C. S., & Noller, H. F. (1995). Suppresion of a cold-sensitive mutation in 16S

Salmonella Cold Stress Response 31