Quorum sensing and its significance

1. Quorum sensing
& its significance
Dr. Harinatha Reddy M.sc, Ph.D.
biohari14@gmail.com
Department of Microbiology
Sri Krishnadevaraya University
Anantapur, A.p. India

2.  More recently it has become clear that many bacteria can
communicate with one another and behave cooperatively. A major
way in which this cooperation is by a process known as quorum
sensing or auto induction.
 Quorum sensing is a process of cell–cell communication that allows
bacteria to share information about cell density and adjust gene
expression.
 Quorum-sensing controls the expression of virulence gene by
pathogenic bacteria..
 Quorum sensing (QS) allows bacteria to restrict the expression of
specific genes to the high cell densities at which the resulting
phenotypes will be most beneficial.
 This is a phenomenon in which bacteria monitor their own
population density through signal molecules, called auto-
inducers.

3.  Quorum sensing was first discovered in gram-negative
bacteria and the most common signals in gram-negative
bacteria are acyl homoserine lactones (AHL) or (HSLs).
 These are small molecules composed of a 4- to 14-carbon
acyl chain attached by an amide bond to homoserine
lactone.
 The acyl chain may have a keto group or hydroxyl group
on its third carbon.
A generalized structure for acyl
homoserine lactone, the best-known
quorum sensing signal or autoinducer.

4.  Acyl AHLs diffuse into the target cell. Once they reach a sufficiently
high level, acyl AHLs bind to special receptor proteins and trigger a
conformational change. Usually the activated complexes act as
inducers that is, they bind to target sites on the DNA and stimulate
transcription of quorum-sensitive genes. The gene needed to
synthesize acyl HSL is also produced frequently, thus amplifying the
effect by the production and release of more autoinducer molecules.
FIGURE:
The receptor protein that acts
as an inducer is labeled R.

5. Many different processes are sensitive to AHLs signals and quorum
sensing in gram-negative bacteria.
Some well-studied examples are
(1) Bioluminescent production by Vibrio fischeri.
(2) Synthesis and release of virulence factors Pseudomonas
aeruginosa:
(3)Conjugal transfer of genetic material by Agrobacterium
tumefaciens.
(4)Antibiotic production by Pseudomonas aureofaciens.
 Gram-positive bacteria also regulate activities by quorum
sensing, often using an oligopeptide signals.
 Good examples are mating in Enterococcus faecalis,
 Stimulation of sporulation by Bacillus subtilis, and
 Production of many toxins and other virulence factors by
Staphylococcus aureus.
 Quorum sensing even stimulates the development of aerial mycelia
and the production of streptomycin by Streptomyces griseus.

6.  An interesting and important function of quorum sensing is to
promote the formation of mature biofilms by the pathogen
Pseudomonas aeruginosa.
 Biofilm formation makes sense for the pathogen because
biofilms protect against antibiotics and detergents.
 Quorum sensing should be very effective within biofilms
because there will be less dilution and acyl HSL levels will
increase rapidly.
 Quorum sensing is an example of what might be called
multicellular behavior in that many individual cells communicate
and coordinate their activities to act as a unit.
 Other examples of such complex behavior is pattern formation in
colonies and fruiting body formation in the myxobacteria

7. THREE TYPES OF AUTO INDUCER
A variety of different molecules can be used as signals. Common classes of
signaling molecules are N-acyl homoserine lactones (AHL) in Gram-
negative bacteria, oligopeptides in Gram-positive bacteria and a family of
auto inducers known as autoinducer-2 (AI-2) in both Gram-negative and
Gram-positive bacteria:
① Acyl-homoserine lactone (AHL): Autoinducer used by Gram (-) bacteria for
intraspecies communication.
② Autoinducer peptide (AIP): Autoinducer used by Gram (+) bacteria for
intraspecies communication.
③ Autoinducer-2 (AI-2): Autoinducer used by many QS bacteria for
interspecies communication.

8. Bacterial QS systems: Acyl-homoserine lactone (AHL):

9. Autoinducer peptide (AIP):
Histidine kinases (HKs) can act as cellular receptors for signaling molecules
in a way analogous to tyrosine kinase receptors. Response regulator (RR)

10.  Auto inducers 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.
 Gram-positive and Gram-negative bacteria use quorum
sensing to regulate physiological activities like symbiosis,
virulence, competence, conjugation, antibiotic production,
motility, sporulation, bioluminescence and biofilm
formation.

11.  Bacteria that use quorum sensing constitutively produce and
secrete certain signaling molecules (called autoinducers or
pheromones). Bacteria also have a receptor that can
specifically detect the signaling molecule (inducer). When the
inducer binds the receptor, it activates transcription of certain
genes, including those for inducer synthesis.
 Activation of the receptor induces the up-regulation of other
specific genes, causing all of the cells to begin transcription at
approximately the same time. This coordinated behavior of
bacterial cells can be useful in a variety of situations.
 For instance, the bioluminescence luciferase produced by
Vibrio fischeri would not be visible if it were produced by a
single cell. By using quorum sensing to limit the production of
luciferase to situations when cell populations are large, V.
fischeri cells are able to avoid wasting energy on the
production of a useless product.

13. VIBRIO FISCHERI
 Quorum sensing was first observed in Vibrio fischeri, a
bioluminescent bacterium that lives as a mutualistic
symbiont in the photophore (or light-producing organ) of the
Hawaiian bobtail squid.
 When Vibrio. fischeri cells are free-living (or planktonic), the
auto inducer is at low concentration, and, thus, cells do not
luminesce. However, when they are highly concentrated in
the photophore (about 1000 cells/ml), transcription of
luciferase is induced, leading to bioluminescence.

14.  In the low nutrient environment of seawater, V. fischeri is present at low
densities; any autoinducer produced by the cells diffuses away rapidly,
and cellular luminescence does not occur.
 However, certain species of marine animals, such as Hawaiian squid
have developed symbiotic relationships with V. fischeri.
 These animals contain light organs where they provide a nutrient rich
environment for the bacteria to grow.
 When V. fischeri grows to a high cell density within the light organ, it
induces expression of the lux genes and produces light. The host animal
uses this light to attract prey or to avoid predation.

15. Quorum sensing and bioluminescence
 The phenomenon of quorum sensing is a common regulatory mechanism
used by a number of bacteria induces specific cellular functions only at a
high cell density.
 The quorum sensing response was observed in the luminescent marine
bacterium Vibrio fischeri in the early 1970s and now serves as a model
system for understanding quorum sensing in Gram negative proteo
bacteria.
 It has been determined that two genes are essential for this type of
regulatory scheme: luxI, which encodes an autoinducer synthase called
LuxI
luxR, which encodes an auto inducer-dependent activator of the
luminescence genes called LuxR.
 The autoinducer molecule produced by LuxI is an acylated homoserine
lactone (3-oxo-hexanoyl-homoserine lactone).
 V. fischeri cells are permeable to the autoinducer, therefore the
compound accumulates within the cells and in the surrounding
environment at equal concentrations.
 When the autoinducer reaches a critical threshold concentration, LuxR-
autoinducer complexes begin to form and the genes responsible for
cellular luminescence (the lux operon) are activated.

16. Figure: Model of quorum sensing in Vibrio fischeri.
Auto inducer is produced by the product of the luxI gene and diffuses into
and out of the cell.
When the population grows to a high cell density, enough auto inducer is
present to bind to and activate the product of the luxR gene.
LuxR, in complex with auto inducer, binds to the lux box to activate
expression of the lux genes, and light is produced.

17. Salmonella enterica:
 Salmonella encodes a LuxR homolog i.e. SdiA, but does
not encode an AHL synthase. SdiA detects AHLs produced
by other species of bacteria like Aeromonas hydrophila.
 When AHL is detected, SdiA regulates the rck operon on the
Salmonella virulence plasmid.
 Salmonella does not detect AHL when passing through the
gastrointestinal tracts of several animal species, suggesting
that the normal microbiota does not produce AHLs.
 However, SdiA does become activated when Salmonella
bacteria colonized with Aeromonas hydrophila.
 Therefore, Salmonella appears to use SdiA to detect the
AHL production of other pathogens rather than the normal
gut flora.

18. Pseudomonas aeruginosa:
 The opportunistic pathogen Pseudomonas aeruginosa
uses quorum sensing to coordinate the formation of
biofilms, exo polysaccharide production and virulence.
 These bacteria can grow within a host without harming
it, until they reach a threshold concentration. Then they
become aggressive, developing to the point at which
their numbers are sufficient to overcome the host's
immune system, and form a biofilm. The biofilm is a
protective layer encasing the bacteria population.
 Garlic and Ginseng experimentally block quorum
sensing in Pseudomonas aeruginosa.
 It is hoped that the therapeutic enzymatic degradation of
the signaling molecules will prevent the formation of
biofilms and possibly weaken established biofilms.
 Disrupting the signalling process in this way is called
quorum sensing inhibition.

19. THANK U……………….