Quorum Quenching

Latest detailed presentation on quorum quenching

1. Quorum Quenching 1 PRESENTED BY, ARNAB GUPTA KABIRAJ M.Sc. MICROBIOLOGY SEMESTER – II ROLL NO – BURMICRO 2016/002 REGISTRATION NO. – 001765 OF2013-14 THE UNIVERSITY OF BURDWAN

2. Quorum Usually refers to the minimum number of members in an organisation, such as legislative body, needed to conduct the business. 2

3. Quorum Sensing The regulation of gene expression in response to fluctuations in cell-population density. 3

4. Quorum S ensing Cell to cell conversation A signalling mechanism in microorganisms Control gene expression Cell density dependent Example: Bacteria and some social insects (ants and honey bees etc.) 4 Marine Bacteria Use Bioluminescence to Lure Zooplankton and Fish

5. Decision M aking Process Quorum sensing can function as a decision-making process in any decentralised system, as long as individual components have: A means of assessing the number of other components they interact with A standard response once a threshold number of components is dtected 5

6. History 6 Research into AHL based quorum sensing Late 1960s Culture media contained an inhibitor of luminescence was removed by bacteria when in large numbers Kempner & Hanson, 1968 Luminescence was initiated by the accumulation of an activator molecule or "autoinducer" Nealson et al , 1970 , Eberhard , 1972 The marine bioluminescent bacteria Vibrio fischeri grown in liquid cultures and it produced light only when large in numbers Greenberg, 1997

7. Why do bacteria talk to each other? 7 For the reason of: Symbiosis Virulence Competence Conjugation Antibiotic production Motility Sporulation Biofilm formation

8. 8 Within and between bacterial species. Example – Pseudomonas aeruginosa,Aeromonas sp., Yersinia, etc . b) Archaea Example - Methanosaeta harundinacea 6Ac c) Between prokaryotes and their eukaryotic host Animal Plant d) Cross talk - Interspecies communication for antibiotic resistance, virulence and biofilm formation Where Quorum sensing occurs?

9. Quorum Quenching Quorum quenching is the process of preventing quorum sensing by disrupting the signalling. This may be achieved by degrading the signalling molecule . Thus, the mechanism that have evolved to interfere with the bacterial cell cell communication in process termed quorum quenching. 9

10. Why Quorum Quenching? Bacterial Virulence: QSI is a potential method for inhibition of bacterial virulence both In-vitro & In-vivo Recent research into quorum sensing system has produced compounds that can disrupt the bacteria’s ability to communicate, thereby disabling or diminishing the bacteria’s ability to become pathogen. Thus, the body is not compromised by any detrimental effects of the bacteria and the body gets enough time to eradicate the bacteria naturally through immune system functions. 10

11. Antibiotic resistance : Now a days most of the bacteria are antibiotic resistant. Penicillin resistant bacteria developed in 1942, just after 2 years of its introduction. 11

12. Signalling Molecules Class Signalling Molecules Strains Gram negative Bacteria Acyl- homoserine lactones (AHLs) V. fischeri & V. harveyi Gram positive Bacteria Oligopeptides Autoinducer (AIPs) B. subtilis & S. aureus Gram negative Bacteria & Gram positive Bacteria Autoinducer-2 (AI-2) E. Coli & V. harveyi 12

13. Signalling Molecules AIP AHL AIP Structure Description Small peptides that r egulates competence and sporulation gene expressions Several types depending on their length of acyl side chain. Able to diffuse through membrane, involved in virulence and biofilm formation. Involve in interspecies communication among bacteria. Synthesis The precursor is modified, processed and an ATP-binding cassette exporter complexes secretes the mature AIP. These are synthesised by an autoinducer synthase LuxI . AI-2 are synthesized by LuxS . 13 Characterisation of signalling molecules

14. Mechanism of AHLs 14 Recognised by a autoinducer receptor/DNA binding transcriptional activator protein LuxR . LusxR binds to the promoter region and initiate transcription of target gene. There is allow likelihood of a bacterium detecting its own secreted inducer.

15. Quorum Q uenching molecule A new class of quorum quenchers with the chemical formula N-[2-(1H-indol-3-yl)ethyl]-urea and N-(2-phenethyl)-urea, which we named yayurea A and B, respectively. Small compounds inhibit both the expression of QS-controlled toxins and other QS-regulated compounds as well as growth in Gram-negative bacteria. 15

16. Mechanism of Yayurea A and B 16 Figure : Yayurea A and B are perceived by V. harveyi LuxN receptor. In vitro studies with the N-acyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds caused opposite effects on phosphorylation to those caused by AHL. This explains the quorum quenching activity.

17. Function of Quorum Quenchers 17 Figure: Schematic presentation of the interference between zoonotic staphylococcal species and Gram-negative bacteria. The excreted compounds, which we named yayurea A and B, were isolated from S. delphini and structurally characterized. They represent new bacterial products, which quench the QS regulation in a wide spectrum of Gram-negative bacteria by stimulating the LuxN -mediated phosphorylation of LuxU . Furthermore, growth of yayurea A and B producing S. delphini is not suppressed by respiratory toxins when co-cultured with P. aeruginosa . This suggests that the quorum quenchers have a function in self-protection and competitiveness in natural environments shared with Gram-negatives.

18. Strategies for quorum sensing inhibition 18 3 strategies can be applied Targeting signal Generation Targeting AHL signal dissemination Targeting the signal Receptor Signal S ignal Signal Signal receptor Signal receptor Signal receptor Signal receptor Signal receptor Signal receptor

19. Conversation between bacteria Quorum sensing Autoinducer Regulate QS-controlled phenotypes Quorum Quenching QS Inhibitors Block Quorum Sensing Pathway 19 Natural QSI Synthetic QSI AHL degradation system To Talk? Or no Not To Talk?

20. Applications Understanding bacteria. To develop new medicines to treat devastating bacterial infection like Cystic fibrosis, Bacteria Endocarditis, etc. Quorum quenching (QQ) is a relevant approach to inhibit bacterial virulence. QQ approaches do not kill bacteria, possibly limiting the emergence of resistance . QQ enzymes, such as lactonases , are promising as they act extracellularly in a catalytic way. 20

21. Advantage of Anti-Quorum Sensing The advantage of this approach for controlling infection is that there are few evolutionary forces that select for resistance. The compounds kill none of the bacteria, any resistant mutations must compete with living, non-resistant individuals. Hence, no survival advantage to the resistant mutations, natural selection does not come into play and resistant strains will be unlikely to occur. QS molecules have potential antimicrobial functionality and are investigated in immunology and oncology. 21

22. Future P erspectives QS inhibitors have provided evidence of alternative method for fighting bacterial infections. QS inhibitors, may replace the antibiotics. QS inhibitors can be isolated from the huge natural pool of chemicals . Quorum quenching inhibit bacterial virulence and do not kill bacteria, possibly limiting the emergence of resistance. 22

23. References Abdelnour , A., Arvidson , S., Bremell , T., Ryden , C. & Tarkowski , A. (1993). The accessory gene regulator ( agr ) controls Staphylococcus aureus virulence in a murine arthritis model. Infect Immun 61, 3879–3885. Thomas, G. Platt. & Clay Fuqua. (2010) . Whats in a name? The semantics of quorum Sensing. 18(9): Microbiol . 383-387. Antunes , L. C. & Ferreira, R. B. (2009). Intercellular communication in bacteria. Crit Rev Microbiol 35, 69–80. Bendiak , G. N. & Ratjen , F. (2009). The approach to Pseudomonas aeruginosa in cystic fibrosis. Semin Respir Crit Care Med 30, 587–595. Otto, M., Sussmuth , R., Jung, G. & Gotz , F. (1998). Structure of the pheromone peptide of the Staphylococcus epidermidis agr system. FEBS Lett 424, 89–94. Smith, D., Wang, J. H., Swatton , J. E., Davenport, P., Price, B., Mikkelsen , H., Stickland , H., Nishikawa, K., Gardiol , N. & other authors (2006). Variations on a theme: diverse N-acyl homoserine lactone-mediated quorum sensing mechanisms in Gram-negative bacteria. Sci Prog 89, 167–211. http://www.sciencedaily.com 23

24. Conclusion Quorum sensing study help us to understand the communication & virulence of certain bacteria and quorum quenching helps us to inhibit the process without killing bacteria & no occurrence of resistance. Hence, an approach to use over antibiotic to fight bacterial infection. 24

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