![• Data: Assessment of synergistic activity of the ethanolic bark extracts
(20μg/mL) and antibiotics [gentamycin and penicillin] on biofilm inhibition
• Result: Synergistic effect is positive in the case of penicillin
Specific aim 2
To understand the influence of time and varying concentration of ethanolic
bark extract of Melia dubia on the combinatorial action with antibiotics.](https://image.slidesharecdn.com/651259b8-2260-4f56-a0c4-f6816c42fda6-150419141004-conversion-gate01/85/Quorum-Sensing-An-Introduction-19-320.jpg)
Quorum Sensing- An Introduction
- 1. Quorum Sensing- The “Bacterial” Talk Sahana V Department of Biosciences and Technology, DIAT 1
- 3. Why it does? Ruby EG, McFall-Ngai MJ. 1992. A squid that glows in the night: development of an animal-bacterial mutualism. J. Bacteriol. 174:4865–70
- 4. How it does? • Symbiotic relationship with Vibrio fischeri • Light organ of the squid • Bio-luminescence Bassler BL, Losick R (2006) Bacterially speaking. Cell 125(2):237–246.
- 5. Quorum sensing • Cell-cell communication mechanism • Density dependent • Produces signaling molecules • Alteration in gene expression- Group behavior 5
- 6. Three step approach Inside the cell Outside the cell
- 7. Development of virulence • Biofilm Formation • Acid Tolerance • Competence Development Antibiotic Production Symbiosis Implications
- 8. Why it is important to us? • Understand the pathogenicity of a bacterial species • A potential target for targeting bacteria against traditional antibiotic • Understand the symbiosis of bacteria with human body • Produce “Pro-quorum sensing” molecules- Enhance the symbiosis
- 9. Category-1 • “Me” - Intraspecies Signal 1 Signal 2 “You” - Interspecies Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99
- 10. Category-2 Gram Negative Passive Diffusion Gram Positive Two component regulated Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99
- 11. Chemical language • Intra Species- Gram Negative • Acyl Homoserine Lactone • Inter Species- The Universal • Auto Inducer peptide- 2 • Intra Species- Gram Positive • Auto Inducer Peptide -1 Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99
- 12. Vibrio fischeri
- 14. Quorum quenching- Making bacteria deaf and dumb • Inhibition of quorum sensing process • Surgical Removal of pathogenesis • Do not threaten bacteria with life-or-death situations • Less likely to yield resistant phenotype Ashima K. et al. Bacterial Quorum Sensing Inhibitors: Attractive Alternatives for Control of Infectious Pathogens Showing Multiple Drug Resistance. Recent Patents on Anti-Infective Drug Discovery, 2013, 8, 68-83
- 15. Low molecular mass Highly Specific Non-toxic to host Non-interfering to basal bacterial metabolism Chemically Stable Requisites for a qs quencher Ashima K. et al. Bacterial Quorum Sensing Inhibitors: Attractive Alternatives for Control of Infectious Pathogens Showing Multiple Drug Resistance. Recent Patents on Anti-Infective Drug Discovery, 2013, 8, 68-83
- 16. Enzy mes Lactases Acylases Oxidoreductases Synth etic Analo gues Thiolactones trAIP-II Lactams Natur al Inhibit ors Pyrogallol Furanone Antibi otics Erythromycin Azithromycin Quorumquenchers Breah L and Michael J. F. Exploiting Quorum Sensing to Confuse Bacterial pathogens. Microbiol. Mol. Biol. Rev. 2013, 77(1):73
- 17. Synergistic Effect Of A Quorum Sensing Blocker And Antibiotics To Control The Oral Adhesion Of Streptococcus Mutans Project member Sahana V Under supervision of Dr. S. Adline Princy Associate Professor, Quorum Sensing Laboratory, SASTRA Hub for Research and Innovation (SHRI), SASTRA University. 17
- 18. • Data: Influence of time of ethanolic bark extract of M.dubia on cell growth and microbial adhesion at the concentration of 20μg/mL • Result: Maximum inhibition is recorded in the adherent phase(12 and 18 hours) Specific aim 1 To understand the influence of time and varying concentration of ethanolic bark extract of Melia dubia on cell growth and biofilm inhibition.
- 19. • Data: Assessment of synergistic activity of the ethanolic bark extracts (20μg/mL) and antibiotics [gentamycin and penicillin] on biofilm inhibition • Result: Synergistic effect is positive in the case of penicillin Specific aim 2 To understand the influence of time and varying concentration of ethanolic bark extract of Melia dubia on the combinatorial action with antibiotics.
- 20. concerns • Assumption 1: • Quorum-sensing systems are actively utilized during infection and are important for virulence. • Assumption 2: • QS is not essential for bacterial growth, inhibition of QS should not exert selective pressure on the bacteria to develop resistance. • Assumption 3: • QS is a good therapeutic target is that the species specificity of most QS systems should reduce the issues of broad-spectrum activity and off-target effects traditionally associated with antibiotic treatment. 1. Smith EE, et al. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. U. S. A. 103:8487– 8492. 2. Schuster M et al. 2003. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum controlled genes: a transcriptome analysis. J. Bacteriol. 185:2066-2079 3. Chugani S, et al. 2012. Strain-dependent diversity in the Pseudomonas aeruginosa quorum-sensing regulon. Proc. Natl. Acad. Sci. U. S. A. 109:E2823–2831.
- 21. Success stories • 1524 patents filed- QS Inhibitors.1 • Treatment of cholera infection was successful.2 • Enzymatic quorum quenching in treatment of plant and pathogens.3 • Co-administering inhibitory synthetic AIPs along with S. aureus bacteria, staphylococcal lesion formation in the skin of mice was reduced or prevented.4 /15 1. Ashima K. et al. Bacterial Quorum Sensing Inhibitors: Attractive Alternatives for Control of Infectious Pathogens Showing Multiple Drug Resistance. Recent Patents on Anti-Infective Drug Discovery, 2013, 8, 68-83 2. Duan F, March JC. 2010. Engineered bacterial communication prevents Vibrio cholerae virulence in an infant mouse model. Proc. Natl. Acad. Sci. U. S. A. 107:11260 –11264. 3. Vanjildorj E,. 2009. Enhancement of tolerance to soft rot disease in the transgenic Chinese cabbage (Brassica rapa L. ssp. pekinensis) inbred line, Kenshin. Plant Cell Rep. 28:1581–1591. 4. Mayville P,et al. 1999. Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. Proc. Natl. Acad. Sci. U. S. A. 96:1218 –1223.
- 22. Bonnie L. Bassler Howard Hughes Medical Institute Investigator Squibb Professor in Molecular Biology Professor and Chair of Molecular Biology Princeton University.
- 23. Thank you