1- quorum sensing

Quorum sensing (QS) is a way for individual cells to exchange information using small
molecules (SMs) that bind sensory proteins and thus directly or indirectly affect transcription and
translation. The binding threshold is assumed to be reached once the growing population, and
hence the concentration of the secreted SM, attains a certain level. In the following, I use the
term 'QS system' to mean a cell-to-cell communication system in unicellular organisms that
functions via the secretion of communication molecules into the environment and their
subsequent binding to sensor proteins. The term ‘communication molecule’ as I use it here refers
to any SM that is secreted by one organism and changes the behaviour of another one. it is not
necessary that the communication molecule synthesis or detection machinery has evolved for this
purpose, although this is often the case. Different systems can be distinguished by the different
types of communication molecule they use, which are normally also associated with different
types of signal synthesis, import and export, reception and response machinery[1]

Despite differences in regulatory components and molecular mechanisms, all known QS systems
depend on three basic principles. First, the members of the community produce AIs, which are
the signaling molecules. At low cell density (LCD), AIs diffuse away, and, therefore, are present
at concentrations below the threshold required for detection. At high cell density (HCD), the
cumulative production of AIs leads to a local high concentration, enabling detection and
response. Second, AIs are detected by receptors that exist in the cytoplasm or in the membrane.
Third, in addition to activating expression of genes necessary for cooperative behaviors,
detection of AIs results in activation of AI production .This feed-forward autoinduction loop
presumably promotes synchrony in the population[2]

2- AUTO INDUCERS QS

is a bacterial cell-cell communication process that involves the production, detection, and
response to extracellular signaling molecules called autoinducers (AIs).8 From a historical
perspective, the most commonly studied autoinducers belong to one of the following three
categories: acylated homoserine lactones (AHLs), used by Gram-negative bacteria (also
sometimes referred to as autoinducer-1 [AI-1]); peptide signals, used by Grampositive bacteria;
and autoinducer-2 (AI-2), used by both Gram-negative and Gram-positive bacteria. There are
also other QS signals that go beyond these classes, including Pseudomonas quinolone signal
(PQS), diffusible signal factor (DSF), and autoinducer-3 (AI-3), and new molecules will
undoubtedly be discovered as the study of quorum sensing expands to species of bacteria yet to
be investigated.9 AIs accumulate in the environment as the bacterial population density
increases, and bacteria monitor this information to track changes in their cell numbers and
collectively alter gene expression. QS controls genes that direct activities that are beneficial
when performed by groups of bacteria acting in synchrony[3,4,5]
Gram-positive bacteria use peptides, called auto inducing peptides (AIPs), as signaling
molecules. Once produced in the cell, AIPs are processed and secreted. When the extracellular
concentration of the AIP is high, which occurs at HCD, it binds to a cognate membrane-bound
two-component histidine kinase receptor. Usually, binding activates the receptor’s kinase
activity, it autophosphorylates, and passes phosphate to a cognate cytoplasmic response
regulator. The phosphorylated response regulator activates transcription of the genes in the QS
regulon. In some cases of Gram-positive bacterial QS, AIPs are transported back into the cell
cytoplasm where they interact with transcription factors to modulate the transcription factor’s
activity and, in turn, modulate gene expression changes. Gram-negative bacteria communicate
using small molecules as AIs. These are either acylhomoserine lactones (AHLs) or other
molecules whose production depends on S-adenosylmethionine (SAM) as a substrate. AIs are
produced in the cell and freely diffuse across the inner and outer membranes. When the
concentration of AIs is sufficiently high, which occurs at HCD, they bind cytoplasmic receptors
that are transcription factors. The AI-bound receptors regulate expression of the genes in the QS
regulon. In some cases of Gram-negative bacterial QS, AIs are detected by twocomponent
histidine kinase receptors that function analogously to those described in the preceding paragraph
for Gram-positive QS bacteria. Dozens of clinically relevant bacteria use QS to regulate the
collective production of virulence factors.[6,7]

3- Mechanisms of bacterial quorum sensing

In order to perform QS, bacteria should possess certain characteristics: (1) be able to secrete
signaling molecule, an autoinducer molecule which identifies the concentration of signaling
molecules; and (2) be able to control the gene expression of cells in response. The principle of
QS is based on the diffusion of signaling molecules. At a low concentration of signaling
molecules they diffuse away, but as the population and cell density increases the concentration of
signaling molecules increases and once the concentration reaches the threshold level it triggers or
controls gene expression [5]. The basic mechanism of QS in bacteria follows three steps; 1. A
specific type of signaling molecule is secreted in the outer space of the cell. 2. Molecule
accumulation takes place with the increase in the cell population. 3. At the final stage, after
reaching the threshold concentration the signaling molecule is sensed by the bacteria and triggers
the series of regulatory activities [7,8]

Bacteria have the ability to control their gene expression at the population level using the
principle of QS. Oligopeptides act as signaling molecules in Gram-positive bacteria. These
signaling molecules are detected either by surface receptors using two-component systems or by
internalization of oligopeptides inside cell using oligopeptide transport. These signaling
molecules then interact with the transcriptional regulators and thus help in controlling the gene
expression . These regulators help in controlling various functions such as virulence,
competence, conjugation, etc. Bacilli, Streptococci, and Enterococci are some of the Gram-
positive bacterial genera in which such a mechanism of gene expression control is observed
[9,10]
 4- QS mechanisms in yeast and dimorphic fungi

Some evidence suggests that the yeast Saccharomyces cerevisiae exhibits a QS type of regulation
mediated by aromatic alcohols derived from amino acids [11]. This budding yeast produces
tryptophol and phenylethyl alcohol to control the formation of pseudohyphae, biofilm formation
[12]and perhaps virulence towards the grapevine Vitis vinifera [13]. Some QSMs that were
discovered first in other fungal species, such as C. albicans, have been subsequently described to
have roles in S. cerevisiae. For example, S. cerevisiae can produce tyrosol [14] and respond to
farnesol two QSMs first characterised in C. albicans as discussed in detail below. On the other
hand, the only fungus from the group of the basidiomycetes with described QS mechanisms is
Cryptococcus neoformans, a human pathogen. This fungus, the aetiologic agent of
cryptococcosis, undergoes cellular changes that result in the appearance of different cellular
types during infection. After capsule enlargement and growth of the whole cell, ‘titan cells’ are
formed [15]. The main virulence factors in this fungus are the formation of the polysaccharide
capsule and melanin accumulation, which are regulated by QS mechanisms described QS
regulation via peptides (QSP1–4) that are secreted outside the cell prior to uptake via the
transporter Opt1. QSP1 is a central signalling molecule that regulates pathogenesis in C.
neoformans, being a direct target of three transcription factors required for virulence. It is known
that QSP1 regulates secreted protease activity and promotes cell wall function at high cell
densities. Here, similar to Gram-positive bacteria, the signal production requires extracellular
processing of the pro-peptide proQsp1 by a cell-associated protease [16]
References

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