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Lactic acid bacteria (LAB) are known for their ability to produce various inhibitors

including metabolic end products such as organic acids, hydrogen peroxide


and bacteriocin (Rajaram et al. 2010; Sankar et al. 2012; Zhou et al. 2014).
The direct application of LAB strains or their antimicrobial products in order to
inhibit unwanted bacteria in food is introduced in the concept of biopreservation
(Stiles1996). Many recent studies and reviews have discussed this issue
extensively (Cleveland et al. 2001; Deegan et al. 2006; Ross et al. 2002).
LAB is the bacteria most often used in fermented foods because it has a
long history of safe use. It is a microbe that lives in the digestive tract of both
humans and animals (Maragkoudakis et al.2009). L. salivariusisolated from
chicken carcasses has the potential to be used as a preservative to increase safety
and to extend the shelf life of chicken products (Sakaridis et al. 2014).
Bacteriosinogenic LAB has been shown to inhibit the growth of pathogenic
and spoilage bacteria in meat (Gálvez et al. 2008; Lücke2000; Díaz-Ruiz et
al. 2012), including in sausage fermentation (Leroy et al. 2006) and some food
products (Bredholt et al. 1999; Buchanan and Bagi1997; Dimitrijevic e ́ t al.
1999; Duffes et al. 1999). Bacteriocin is an alternative bio preservative
compound produced by LAB that can be used in foodashavingbactericidal
properties against Gram-positive and Gram-negative bacteria.It is thus very
beneficial for the food industry because of its activity of inhibiting the growth
of the disease-carrying bacteria that are usually present in food. Bacteriocin
has the potential to act as a natural preservative to replace chemical
preservatives in food. Enterococcus, Lactobacillus, Pediococcus, Leuconostoc,
and Carnobacteriumare genera of LAB that commonly produce bacteriocin
(Eijsink et al. 2002). Nisin is produced by Lactococcuslactissubsp. lactishas been
used for commercial food preservation. Hosono et al. (1989) isolated 4
genera of LAB from dadih, a fermented food made from buffalo milk similar
to yogurt, namely Lactobacillus sp., Streptococcus sp., Leuconostoc sp.and
Lactococcussp. Dadih's LAB has never been studied for their antimicrobial
activity before even though these strains have an anti-mutagenic ability against
various mutagen compounds (Hosono et al. 1990). The purposes of the
present study wereto evaluate the ability of BAL isolated from dadih to inhibit
the growth of Listeria monocytogenes and to determine the type of antimicrobial
compounds involved

Global antibiotic consumption in livestock was estimated to be approximately 63,000 to over 240,000
metric tons yearly (World Bank, 2017), and these quantities may certainly increase because of the high
consumption level registered in the emerging economies (World Bank, 2017). However, a substantial
decline of the sales of antimicrobials for food-producing species has been observed in some countries
(ESVAC, 2017). As a consequence, this overuse of antibiotics will contribute to spreading antimicrobial
resistance worldwide Antibiotics can affect the intestinal microbiota and host physiology by (i)
preventing pathogen colonization, (ii) impacting the immune system, (iii) increasing fat absorption by
decreasing the hydrolysis of conjugated bile salts, and (iv) enhancing the use of nutrients as a result of
an alteration of the intestinal wall and lamina propria (Niewold, 2007; Lee et al., 2011). The balance
existing between beneficial and non-beneficial bacteria in the gastrointestinal tract (GIT) of a healthy
animal can be modified upon alteration of the bacterial proportions causing pathogen infections from
different external sources (Kers et al., 2018; Pluske et al., 2018). Pathogenic bacteria can negatively act
on the animal health and welfare, as well as on their growth and reproduction performances. Some of
these can reach the human gastrointestinal tract through the food chain (Newell et al., 2010), which
meanwhile can lead to antibiotic resistance transmission (Soucy et al., 2015). Resistance to antibiotics is
a serious concern for humanity.

Lactic acid bacteria are suitable for livestocks as probiotics because of their capabilities to modify the
environment, in which they have been delivered, by producing different metabolites among which a
wide range of inhibitory substance and even competitive exclusion (Gaggìa et al., 2010; FAO, 2016). It
should be noted that LAB-probiotics belong to Lactobacillus (Lb.), Pediococcus (Ped.), Lactococcus (Lc.),
Enterococcus (Ent.), Streptococcus (Str.), and Leuconostoc (Leuc.) species. Nevertheless, Lactobacillus
species remain the upmost studied and used ones (Martínez Cruz et al., 2012). Mechanisms of
pathogens inhibition by LAB-probiotics include (i) production of inhibitory compounds, (ii) prevention of
the pathogens adhesion, (iii) competition for nutrients, (iv) modulation of the host immune system, (v)
improvement of nutrient digestibility, feed conversion, and (vi) reduction of toxin bioavailability(Nuria
Vieco-Saiz1,2 , Yanath Belguesmia1 , Ruth Raspoet2 , Eric Auclair2 , Frédérique Gancel1 , Isabelle
Kempf3,4 and Djamel Drider1 )

There is growing concern over the rise of antibiotic-resistant microorganisms and the likely inefficiency
of current therapies in the near future. These problems highlight the need to search for alternative
strategies. Bamgbose Timothy1,2,*, Atta Habiba Iliyasu2 and Anupkumar R. Anvikar1

The uncontrolled use of effective antibiotics such as penicil-lins, cephalosporins, tetracycines,


macrolides, metronida-zole, clindamycin, and carbapenems has raised a variety of concerns and
disputes and led to an increase in antibiotic -resistant bacteria. In recent years, antibiotic misuse, and
overuse, as well as inadequate infection treatment in peo-ple and animals, have accelerated the spread
of antibiotic-resistant bacteria (Llor etal., 2014). Bacteria have devel-oped resistance to the drugs
used to treat them by decreasing or eliminating the effectiveness of antibiotics provided by doctors and
other healthcare professionals. Antibiotic resist-ance has increased considerably because of the
treatment of livestock or food animals with antibiotics identical to those used to treat human sickness,
resulting in the transmission of resistant bacteria to humans. In recent decades, antibi-otic-resistant
bacteria have posed the biggest danger to food security and global health (Landers et al., 2012). Due
to the slow rate of discovery of new broad-spectrum antibiotics, researchers found a possible alternative
by using substances generated from beneficial bacteria to kill harmful bacteria.Bacteriocins are getting
more interest as possible clini-cal antimicrobials and immune modulating agents, notwith-standing their
traditional usage as food preservatives (John-son et al., 2018). Bacteriocins, due to their broad or
narrow spectrum efficacy against antibiotic-resistant bacteria, may become an effective solution. To
illustrate, bacteriocins produced by Gram-positive bacteria are largely inhibitory to Gram-positive
bacteria and less effective against Gram-negative bacteria. However, it is different for RX7 bacteri-ocin,
which was obtained from a soil sample and produced by Bacillus amyloliquefaciens strain RX7. This RX7
bacte-riocin show broad spectrum of activity where is can be used against both Gram-positive and
Gram-negative bacteria as well as fungus. RX7 bacteriocin can inhibits the growth of Listeria
monocytogenes, Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa,
Salmo-nella enteritidis, and Salmonella gallinarum as well as Can-dida albicans. Example of narrow-
spectrum bacteriocins

The discovery of antibiotics represents a major achievement in the management of infectious diseases,
and has greatly enhanced quality of life and life expectancy all over the world. However, antimicrobial
resistance (AMR) rapidly emerged a few years after the use of antibiotics, and its continuous spread has
since been a major health problem [1]. Multidrug- and even pandrug-resistance to the main classes of
antibiotics commonly used in clinical practice is increasingly noted for both Gram-positive bacteria (GPB)
and Gram-negative bacteria (GNB) [1]. The continuously growing rate of morbidity and mortality
associated with Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococci
(VRE) or Multidrug-Resistant (MDR) GNB present a serious health and economic burden in both hospital
and community settings, highlighting the need to develop new antibiotics [2–4]. It was understood that
the solution comes with the rational use of already-existing antibiotics. However, in the race against
microbial resistance, pressing efforts have been made in order to develop new antimicrobial agents [5].
( Alexis Simons 1,2,* ,† , Kamel Alhanout 1,† and Raphaël E. Duval 1,3,)

WHO (2019) melaporkan bahwa penyakit yang disebabkan oleh patogen Multidrug resistant (MDR)
merupakan salah satu masalah besara di dunia Kesehatan (WHO, 2019). Banyaknya patogen yang
resisten terhadap antibiotik menyebabkan menurunnya keefektifan penggunaan antibiotik secara global
(Gupta and Datta, 2019). Mariam rima (2)(2021) melaporkan bahwa Multidrug resistensi (MDR) dan Pan
Drug Resistensi (PDR) menjadi salah satu penyebab utama dalam peningktan angka morbiditas dan
mortalitas di seluruh dunia. Oleh karena para peneliti terus melakukan identifikasi terhadap submer
antimikroba baru yang dapat dijadikan sebagai kandidat yang dapat menggantiakn peran antibiotik.

Lactic acid bacteria (LAB) have been known since ages for their use in traditional fermented foodstuff
owing to their capability to bring enviable changes in flavor, taste and for inhibiting food spoiling
pathogenic microorganisms, thus making them an attractive natural biopreservative [1]. LAB are in
general considered to be food grade microorganisms and assumed to be secure for human consumption
as they get degraded when they come in contact with human gut by the action of proteases; hence, also
contemplated as generally regarded as safe (GRAS) organisms. These are known to show preservative
effect owing to their capability to produce hydrogen peroxide, organic acids, diacyls, and bacteriocins.
Among all these, the antimicrobial compounds, bacteriocins, have received a greater attention as
natural preservatives because nearly all of them are heat tolerant up to a particular temperature range
and are amenable to proteolytic inactivation [1]. The bacteriocins are known to be produced by both
positively and negatively Gram stained bacteria, however, the highest number of bacteriocins studied
and identified are reported to be the antimicrobial peptides of Gram positive bacteria (Parveen
Kaur Sidhu and Kiran Nehra)

Bakteri asam laktat telah lama diketahui memiliki kemampuan dalam menghasilkan berbagai senyawa
penghambat bakteri patogen seperti asam organic, hydrogen peroksida, dan bakteriosin.
Lactic acid bacteria (LAB) are known for their ability to produce various inhibitors
including metabolic end products such as organic acids, hydrogen peroxide
and bacteriocin (Rajaram et al. 2010; Sankar et al. 2012; Zhou et al. 2014).

According to the WHO, diseases caused by multidrug-resistant (MDR) pathogens are a serious
worldwide public health problem (World Health Organization, 2019c). The rapid spread of MDR
pathogens have reduced the effectiveness of common antibiotics (Gupta and Datta, 2019). Therefore,
there is a particular need for the development of new antimicrobial agents, specifically those directed
against MDR bacteria (Fair and Tor, 2014). Bacteriocins represent the most important group of
antimicrobial peptides with applications in human health (Marshall and Arenas, 2003). The ability of
bacteriocins to kill or inhibit relevant pathogenic bacteria (including MDR pathogens) in vitro has been
well documented (Cui et al., 2012; Gabrielsen et al., 2014; Perez et al., 2014; Newstead et al., 2020).
( Diego Francisco Benítez-Chao1,2† , Angel León-Buitimea1,2† , Jordy Alexis Lerma-Escalera1,2 and José
Rubén Morones-Ramírez1,2 *)

At the present, in 2021, multidrug-resistant (MDR) and even pandrug-resistant (PDR) bacteria have
spread widely around the world and are currently responsible for increasing morbidity and mortality
rates, as well as the significant cost to society [2]. The low frequency of discoveries of new classes of
antibiotics, and the rapid emergence of resistance to novel antibiotics, show the need for novel
therapeutic alternatives to antibiotics, such as lysine-based small molecules, vaccines, anti-virulence
strategies, phage therapy and antimicrobial peptides. Antimicrobial resistance (AMR) is an emerging
global health problem that results, in some cases, in difficulties to treat bacterial infections. It was listed
by the World Health Organization (WHO) among the top ten global public health threats facing
humanity, as it is predicted to cause about 10 million deaths each year by 2050 [3]. Therefore, efforts to
slow down the propagation of AMR have been implemented worldwide As such, a Global Action Plan on
Antimicrobial Resistance (GAP) was created in 2015, aiming to implement national action plans to limit
the progress of AMR. In addition, the WHO reports call for urgent action to avert an antimicrobial
resistance crisis and insists on the importance of discovering and developing new antibiotics. Thus, new
compounds that are active against pathogens, especially those which cause nosocomial infections and
tend to adopt multidrug resistance, are needed. To curb this problem, several alternative therapies have
been proposed, among which antimicrobial peptides (AMPs) were suggested to be very promising more
than 20 years ago, as they have existed in nature for millions of years with almost no or limited
resistance development [4]. This makes them very attractive compared to antibiotics that develop
resistance relatively fast. This absence/slow development of resistance against microbes may be
attributed to the presence of various modes of action of AMPs against the bacteria in comparison to the
fixed targets used by the antibiotics [5]. In addition, AMPs are considered less toxic, as they are broken
down into amino acids unlike other therapeutics, which might generate potentially harmful metabolites.
This review is to highlight where these molecules stand now in the overall scheme to curb MDR bacterial
infections. Their potential to counteract AMR, to replace traditional antibiotics, to evaluate their
benefits and to describe the challenges faced by R&D will be discussed in this review. AMPs are small
polypeptide molecules, typically made up of around 12 to 50 amino acids, found in all classes of living
organisms [6]. These molecules are produced as secondary metabolites, are part of the innate immunity
and are, in mammals, usually ribosomally produced by epithelial cells, but also by phagocytes (cells of
the immune system). (Mariam Rima, Mohamad Rima, Ziad Fajloun, Jean-Marc Sabatier, Burkhard
Bechinger and Thierry Naas)

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