1. QUORUM SENSING Presented By Anu Mehta Ph.D. II year
Animal Biochemistry Division 1 1

2. Communication in Bacteria
In bacteria, communication can be mediated by different chemical signals
These signals can be either related to:
Cell density (population) -- Quorum sensing signals
Different stages of growth -- e.g. Indole etc. 2 2

3. What is QUORUM? and QUORUM SENSING is....
Literally 'quorum' depicts a situation for -
a minimum number of members that must be present to constitute a valid meeting
In scientific terms......it represents
THRESHOLD population density
and QUORUM SENSING is....
The term quorum sensing has been employed to describe a density dependent communication phenomenon. 3 3

4. DISCOVERY in late 1970s
Originally discovered in the luminiscent bacterium Vibrio fisheri
Exists as free living cells or as symbionts in the light producing organ of an animal host such as Hawaiian bobtail squid 4 4

5. and then after 15 years ago......
EP Greenberg and collegues termed Quorum Sensing as the secretion and perception of small signalling molecules that in turn are transduced to coordinate a behaviour of a minimal unit of microorganisms. 5 5

6. Vibrio fisheriCLASSICAL EXAMPLEthe discovery organism
Mechanisms involved in bacterial QS
(Source- 6 6

7. QUORUM SENSING SIGNALS molecular terms
Depending upon Gram +/- bacteria 2 major classes have been defined :
AUTO INDUCER PEPTIDE SIGNALS
AUTO INDUCER NON PEPTIDE SIGNALS
GRAM POSITIVE
GRAM NEGATIVE 7 7

8. QUORUM SENSING SIGNALS molecular terms
AUTO INDUCER PEPTIDE SIGNALS
AUTO INDUCER NON PEPTIDE SIGNALS 8 8

9. SENSING WITH DIFFUSIBLE SIGNALS acyl-homoserine lactone (HSL)9 9

10. SENSING WITH NON DIFFUSIBLE SIGNALS Auto Inducer Peptides(AIPs)10 10

11. SENSING CIRCUIT ARCHITECHTURE
Parallel
Series 11 11

12. PARALLEL ARRANGEMENT
All 3 signals HAL-1, AI-2, Cal-1 converge on LuxO that activates LuxR
through a series of steps in the regulation of target genes 12 12

13. SERIES ARRANGEMENT
One signal 30-C12-HSL activates a set of target genes, including the
synthase for producing the second signal C4-HSL, which in turn acivates
a different set of target genes 13 13

14. SPECIFICITY IN SIGNALING to inter-, intra- species and interkingdom communications
When and why specificity is required?
How specificity is achieved?
Specificity with multiple signals and how crosstalks mediated through quorum sensing?
Do non specific signals are also involved somehow and somewhere? 14 14

15. WHEN AND WHY SPECIFICITY IS REQUIRED?
In case of autoinducer-mediated signalling, there is high specificity for the signal to its cognate receptor
It is required and essentially important in case of pathogenic bacteria, where the expression of different virulence genes needs to be coordinated for infection 15 15

16. HOW SPECIFICITY IS ACHIEVED?
Can be achieved
specificity in binding interactions between each autoinducer signal and LuxR-like receptor or
regulation of activated LuxR binding to the promoter of target genes 16 16

17. continued......
Composition and structure of the signals are also important in maintaining specificity of signaling
Structural analysis of cognate receptor-acyl-HSL pairs indicates that the acyl side chain of autoinducer signals is a key determinant of the specificity observed in autoinducer signaling
Differences in length, structure and substitutions in the acyl side chain groups can impact the binding between autoinducers and LuxR-like proteins, and thereby quorum sensing- related signaling 17 17

18. continued...... In case of Gram + bacteria :
most AIP signals have a core peptide whose sequence is not conserved and can be modified differently by different bacteria
specificity is achieved through binding of the signal and sensor kinase on the cell surface 18 18

19. SPECIFICITY WITH MULTIPLE SIGNALS AND CROSS TALK
Example :
V.harveyi produces 3 autoinducer signals HAI-1, AI-2 and CAI-1 that use same cognate receptors
P.aeruginosa produces 2 acyl-HSL based autoinducers and quinolone based signals too
THESE SIGNALS NEED NOT BE SIMILAR 19 19

20. continued......
Here is the requirement of some degree of non specific signaling
Non specific signal mediated interactions include
recognition of a signal produced by a different bacterium
interference with processing of autoinducer signals through competition 20 20

21. CROSS TALK IS UNIDIRECTIONAL
continued......
Recognition of a signal produced by a different bacterium
Interaction between P.aeruginosa and B.cepacia that are found in lungs of cystic fibrosis patients
CROSS TALK IS UNIDIRECTIONAL 21 21

22. continued...... No impact on cell growth but disrupts
Interference with processing of autoinducer signals through competition
AIP produced by one strain of S.aureus interferes with other S.aureus in
addition to upregulating virulence genes in its own species.
No impact on cell growth but disrupts
the activation of virulence genes 22 22

23. INTERKINGDOM SIGNALING
Bacterial world Eukaryote world 23 23

24. EXAMPLES interactions with animals via QS
~ 1014 commensal bacteria are present in the human GIT
> 500 bacteria species are thought to present in the human oral cavity
YES, some form of communication underlies their coexistence in complex environments. 24 24

25. continued....
Microbes do respond to the host signals and host can also recognise the microbial signals...enabling them to act as pathogens
E. coli O157:H7 is an enteric pathogen
Infective dose quite low ~ CFU mL-1
Norepinephrine and epinephrine exposure to this strain is involved in cross talk with bacterial QS pathways
Chemotaxsis, motility and colonization of the pathogen relies on utilising other bacterial or host signals 25 25

26. EXAMPLES interactions with plants via QS
Interactions between bacteria and plant derived signals have also been reported
A. tumefaciens crown gall disease 26 26

27. continued.... Bacteria bind to tumor derived molecules
Expression of luxR- like protein TraR
TraR upregulates regulation of a tumor inducing plasmid and its transfer into plant cells
Bacteria utilize major plant hormone IAA as a source of C, N and
energy, hence......prokaryotes utilize
specific hosts and even to initiate disease states 27 27

28. EXAMPLES 28

29. CAN WE EXPLOIT QUORUM SENSING ???
YES!!!!
From quorum sensing to quorum quenching for antimicrobial drug therapy
mice treated with furanones decreased P.aeuroginosa cells in infected lung tissues
Delesia pulchra 29 29

30. continued.... and the list is endless……. Computing and robotics
improving the function of self organising networks
Using probiotic bacteria as dietary supplements in health promoting foods
B.subtilis produces a QS signal CSF (competence and sporulation stimulating factor), activates Hsp27 in intestine which protects from oxidative damages dysentry treatment
and the list is endless……. 30

31. CONCLUSIONS
QS enables bacteria to indulge in specific communications between themselves. This process in turn helps the total community to grow stronger.
As the regulation takes place at the gene and molecular level, this enhances the possibilities of manipulations of the original QS principle which can be further utilized for human benefits like to cope up with novel antimicrobial drugs and other potential therapeutics 31 31

32. REFERENCES
Bhattacharyya, I. and Chaudhary, M. Quorum Sensing- Let Bacteria Talk. Advanced Biotech 2008;Mini Review:
Gera, C. and Srivastava, S. Quorum sensing: The phenomenon of microbial communication. Curr Sci 2006; 90: 5
Jayaraman, A. and Wood, T.K. Bacterial Quorum Sensing: Signals, Circuits, and Implications for Biofilms and Disease. Annu. Rev. Biomed. Eng. 2008;10:
March, J.C. and Bentley, W.E. Quorum sensing and bacterial cross- talk in biotechnology. Curr Opin Biochem Bioeng 2004; 15: 32 32

33. Suggestions welcomed 33 33

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