QUORUM SENSING- THE “BACTERIAL” TALK

Sahana V

Department of Biosciences and Technology,

DIAT

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THE HAWAIIAN BOBTAIL SQUID

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WHY IT DOES?

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Ruby EG, McFall-Ngai MJ. 1992. A squid that glows in the night: development of an animal-bacterial mutualism. J. Bacteriol. 174:4865–70

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HOW IT DOES?

• Symbiotic relationship with Vibrio fischeri

• Light organ of the squid

• Bio-luminescence

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Bassler BL, Losick R (2006) Bacterially speaking. Cell 125(2):237–246.

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QUORUM SENSING

• Cell-cell communication mechanism

• Density dependent

• Produces signaling molecules

• Alteration in gene expression- Group behavior

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THREE STEP APPROACH

Production of signalsAccumulation of signals

Sensing by siblings / cousinsInside the cell

Outside the cell

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IMPLICATIONS

Development of virulence• Biofilm Formation• Acid Tolerance• Competence Development

Antibiotic ProductionSymbiosis

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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

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CATEGORY-1• “Me” - Intraspecies

Signal 1 Signal 2

“You” - Interspecies

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Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99

10CATEGORY-2Gram Negative

Passive Diffusion

Gram Positive

Two component regulated

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Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99

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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

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Miller MB, Bassler BL. Quorum sensing in bacteria. Ann Rev Microbiol 2001; 55:165-99

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Vibrio fischeri

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Streptococcus mutans

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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

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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

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REQUISITES FOR A QS QUENCHER

Low molecular mass Highly Specific Non-toxic to

host

Non-interfering to basal bacterial

metabolism

Chemically Stable

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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

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EnzymesLactasesAcylasesOxidoreductases

Synthetic Analogue

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ThiolactonestrAIP-II

Lactams

Natural Inhibitors

PyrogallolFuranone

Antibiotics

ErythromycinAzithromycin

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QU

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QU

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CH

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Breah L and Michael J. F. Exploiting Quorum Sensing to Confuse Bacterial pathogens. Microbiol. Mol. Biol. Rev. 2013, 77(1):73

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.

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• 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 1To understand the influence of time and varying concentration of ethanolic

bark extract of Melia dubia on cell growth and biofilm inhibition.

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• 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 2To understand the influence of time and varying concentration of ethanolic

bark extract of Melia dubia on the combinatorial action with antibiotics.

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CONCERNS

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• 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.

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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

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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, 68-832. 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.

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Bonnie L. BasslerHoward Hughes Medical Institute InvestigatorSquibb Professor in Molecular BiologyProfessor and Chair of Molecular BiologyPrinceton University.

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THANK YOU

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