SlideShare a Scribd company logo
1 of 38
Molecular Basis of Quorum Sensing in
Virulence of Bacterial Pathogens
Tuesday, May 31, 2016 1
Shezaib Siddiqui
Research Fellow
 Introduction
 What is Quorum Sensing?
 Molecular basis of infections
a. Staphylococcus aureus
b. Pseudomonas aeruginosa
 Biosynthesis and degradation of Quorum sensing
 Therapeutic approaches
2
3
KEY TERMS
Pathogenicity:
The ability of an organism to cause a disease.
Virulence:
The degree of pathogenicity or disease caused by a pathogen.
OR
Total no. of pathogenic determinants an organism is
collectively termed as virulence.
4
 Phenomenon that regulates the gene expression of
bacterial population in unison at particular density in
response to secreted chemical molecules.
OR
 Synchronous gene expression of bacterial population in
an environment.
5
HISTORY
o First Identified in late1960s by Nealson et
al.
o Discovered in Vibrio fischeri and Vibrio
harveyii
o V. fischeri is a symbiotic microbiota of
Howaiian bobtail squid light organ.
o V. Harveyi is a free living marine bacterium
o Bioluminescence in Vibrio is control via
Quorum sensing (QS).
o Lux operon was discovered as QS
regulatory coding region.
6
Howaiin bobtail squid
Vibrio fischerii
Vibrio harveyi
Quorum Sensing in a Nut Shell
Production and release of signalling molecule (Auto inducer).
Diffusion of Auto inducer (AI) molecule at low cell density leaving the QS
circuit in-active
Activation of QS circuit by AI at higher concentration due to Higher
cell density.
Transcriptional activation of down regulating genes by AI receptor
complex or other activated signalling molecule.
Activation of virulence, biofilm formation, sporulation, competence and
antibiotic production.
7
QS IN GRAM NEGATIVE
BACTERIA
 The autoinducers are typically
molecules called acyl-
homoserine lactones
(AHLs).
 AHLs diffuses extracellular
and intracellular via passive
transport.
QS IN GRAM POSITIVE
BACTERIA
 The autoinducers are
oligopeptides, short peptides
typically 8-10 amino acids
long.
 Oligopeptides excretes in
extracellular environment via
active transport.
8
Schematic Representation of QS Circuits
Canonical bacterial quorum-sensing (QS) circuits. Autoinducing peptide (AIP) QS in Gram-
positive bacteria by (A) two-component signalling, or (B) an AIP-binding transcription factor.
Small molecule QS in Gram-negative bacteria by (C) a LuxI/LuxR-type system, or (D) two-
component signalling.
Gram
positive
Gram
negative
QS Circuit of Vibrio harveyi
Lux Bioluminescence System
11
12
 S. aureus is a gram positive opportunistic pathogen.
 Causative agent of many cumbersome respiratory and skin
infections and poisonings.
 Few of high mortality infections and poisonings are Scalded
skin syndrome, toxic shock syndrome, furuncles, carbuncles,
sinusitis, otitis media etc.
 Emerged as Multi drug resistant bug and many hospital setting.
 Prevalent in > 60% of Nosocomial infections
 MRSA has mortality rate of >20%
13
 Encode various virulence factor under the control of Quorum
sensing system (Agr operon)
14
Scalded Skin Syndrome Impetigo
Toxic shock syndrome Otitis media
 S. aureus has a peptide based quorum sensing system ,encoded
by accessory gene regulator (agr) locus.
 The agr locus controls transcription of two RNA transcripts
RNA II and RNA III from promoter P2 and P3, respectively.
 RNA II encodes Agr A, B, C and D proteins
 RNA III encodes δ-hemolysin and posses regulatory activity.
15
Protein Function
Agr A Transcription factor (Activated
by Agr C)
Agr B Triming and transport of pre-
AIP (Agr D)
Agr C Histidine Kinase recetor of
AIP
Agr D Pre- Auto inducer peptide
Table 1: components of agr system
The Agr System
16
QS Circuit of Staphylococcus aureus
Role of RNAIII in virulence:
 5’ end upregulates transcription of α- hemolysin.
 3’ end is responsible for the repression of rot (repressor of
toxin) protein and Protein A.
 Rot inhibits the transcription of various toxins.
 Inhibition of rot upregulates the translation of toxins and
increases virulence.
 Repression of Protein A (cell surface protein) decease
adhesion of biofilm.
17
Role of Agr in Biofilm control:
 Agr A up regulates the translation of PSMs (Phenol
soluble modulins).
 PSMs are peptide toxin that help in channel formation
in tissues.
 PSMs also acts as surfactants that allow biofilm
dispersal.
 Biofilm dispersal helps S. aureus to colonize and infect
new sites.
18
Polymorphism in Agr Locus
 S. aureus can be classified in to 4 distinct groups based
on Agr locus.
19
Agr locus
Agr I Agr II Agr III Agr IV
Pseudomonas
aeruginosa
20
 P.aeruginosa is a Gram-negative opportunistic pathogen.
 Responsible for severe nosocomial infections cellulitis, UTIs,
endocarditis and epidermidis bullosa.
 Accounts for more than 10% of nosocomial infections.
 Patients with Cystic Fibrosis, injuries (especially burns/boils) are
highly susceptible to P. aeruginosa infections.
 Second leading cause of ventilator associated pneumonia.
 Difficult to treat due to emerging drug resistance.
21
22
Cellulitis Epidermidis bullosa
Endocarditis
23
• Three QS circuits are identified
• LasI/R (3-0C12HL synthase/ Receptor)
• RhlI/R (C4HL synthase/ Receptor)
• Pseudomonas Quinolone Signal (PQS)
Las Inducer/Repressor (I/R) system:
• Auto-induced by LasI
• Controls RhlR operon
• Activates transcription of Las B (Elastase), LasA (Protease), tox A
(Exotoxin A) and aprA (alkaline phosphatase).
• LasI inhibits Rhl R.
RhlI/R system:
 Upregulates rhl I
◦
 Positive regulator of Las B (elastase), RhlA and B
(Rhamnosyl transferase), RpoS (Stationary phase σ
factor) and Pyocanin (niche molecule)
24
25
 Negative regulation NFκB.
 Induces apoptosis in macrophages.
 Down regulates TNF-α and IL-12.
 Induces IL-8 from human bronchial epithelial cells.
26
Biosynthesis and degradation of Acyl Homo serine Lactones
27
Fatty acid
pathway
AHL
synthase
28
Types of Auto inducers in gram negative bacteria
PAME= propionyl amphotericin B methyl ester, DSF= Diffusible signal factor, THMF= tetra hydroxyl methyl furan
29
 Novel therapeutic tartest against multi drug resistant bacteria.
 Reported to decrease virulence only, thus empower host
immune system to combat attenuated pathogen.
 Low chances of drug resistance against quorum quenchers as
they do not kill bacteria.
30
Strategies for Quroum Sensing Inhibition
1. Elimination of signal
 By stimulating enzymatic degradation of auto inducer
 By inhibition of auto inducer biosynthesis and receptor
molecule biosynthesis
2. Inhibition of signal receptor complex
 By using auto inducer analogues
 By treating with antibodies against auto inducer
31
Current Approaches for QS inhibition
 AHL acylases, paraxonases and AHL lactonases are secreted
by many bacteria to degrade AHL , therefore negatively
control QS.
 AHL and AIP analogues have been synthesized to inhibits QS
in S. aureus, P. aeruginosa and other pathogens
 Synthesis of inhibitor molecules against enzymes involved in
AHL biosynthesis, eg: tricolsan inhibits enoyl-ACP reductase.
 Inhibition of auto inducer receptors by using RNAi
technology.
32
33
34
Auto Inducer and Inhibitors of P. aeruginosa
35
Auto inducers and analogue Inhibitors of S. aureus
s
 QS circuits serve as new and potential anti virulence
target to control infections with reduces risks of
resistance evolution.
36
 Miller, Melissa B., and Bonnie L. Bassler. "Quorum sensing in
bacteria."Annual Reviews in Microbiology 55.1 (2001): 165-199.
 Waters, Christopher M., and Bonnie L. Bassler. "Quorum sensing: cell-to-
cell communication in bacteria." Annu. Rev. Cell Dev. Biol. 21 (2005):
319-346.
 Whiteley, Marvin, Kimberly M. Lee, and E. P. Greenberg. "Identification of
genes controlled by quorum sensing in Pseudomonas
aeruginosa."Proceedings of the National Academy of Sciences 96.24
(1999): 13904-13909.
 Bassler, Bonnie L. "How bacteria talk to each other: regulation of gene
expression by quorum sensing." Current opinion in microbiology 2.6
(1999): 582-587.
 Yarwood, Jeremy M., et al. "Quorum sensing in Staphylococcus aureus
biofilms." Journal of bacteriology 186.6 (2004): 1838-1850.
 Rutherford, Steven T., and Bonnie L. Bassler. "Bacterial quorum sensing:
its role in virulence and possibilities for its control." Cold Spring Harbor
Perspectives in Medicine 2.11 (2012): a012427.
37
38

More Related Content

What's hot

Quorum sensing group 6
Quorum sensing group 6Quorum sensing group 6
Quorum sensing group 6Arnab Mullick
 
Quorum Quenching
Quorum QuenchingQuorum Quenching
Quorum QuenchingStudent
 
Human Microbiome
Human Microbiome Human Microbiome
Human Microbiome rashmiakula
 
Bacteria Talk Sense
Bacteria Talk SenseBacteria Talk Sense
Bacteria Talk SenseMicrobiology
 
Quorum sensing in luminescent bacteria
Quorum sensing  in luminescent bacteriaQuorum sensing  in luminescent bacteria
Quorum sensing in luminescent bacteriaSmruti Prabhudesai
 
Microbial interaction.pptx
Microbial interaction.pptxMicrobial interaction.pptx
Microbial interaction.pptxAnurAg Kerketta
 
Thermal Stress and the Heat Shock Response in Microbes
Thermal Stress and the Heat Shock Response in MicrobesThermal Stress and the Heat Shock Response in Microbes
Thermal Stress and the Heat Shock Response in MicrobesAmna Jalil
 
Myxobacteria, life cycle, genetic basis of differentiation
Myxobacteria, life cycle, genetic basis of differentiationMyxobacteria, life cycle, genetic basis of differentiation
Myxobacteria, life cycle, genetic basis of differentiationNeha Sharma
 
Quorum sensing in bacterial populations
Quorum sensing in bacterial populationsQuorum sensing in bacterial populations
Quorum sensing in bacterial populationsKhaled Touny
 
Isolation of antibiotic resistance mutant by replica plating
Isolation of antibiotic resistance mutant by replica platingIsolation of antibiotic resistance mutant by replica plating
Isolation of antibiotic resistance mutant by replica platingbenazeer fathima
 
Type iii bacterial secretion system
Type iii bacterial secretion systemType iii bacterial secretion system
Type iii bacterial secretion systemshiney chatak
 
Starvation Stress Response (Bacterial)
Starvation Stress Response (Bacterial)Starvation Stress Response (Bacterial)
Starvation Stress Response (Bacterial)Tejaswini Petkar
 

What's hot (20)

Quorum Sensing
Quorum SensingQuorum Sensing
Quorum Sensing
 
Quorum sensing group 6
Quorum sensing group 6Quorum sensing group 6
Quorum sensing group 6
 
Quorum Quenching
Quorum QuenchingQuorum Quenching
Quorum Quenching
 
Secretion Systems of Bacteria
Secretion Systems of Bacteria Secretion Systems of Bacteria
Secretion Systems of Bacteria
 
Biodiversity and Microbial Biodiversity
Biodiversity and Microbial BiodiversityBiodiversity and Microbial Biodiversity
Biodiversity and Microbial Biodiversity
 
Human Microbiome
Human Microbiome Human Microbiome
Human Microbiome
 
Bacteria Talk Sense
Bacteria Talk SenseBacteria Talk Sense
Bacteria Talk Sense
 
Quorum sensing
Quorum sensingQuorum sensing
Quorum sensing
 
Quorum sensing in luminescent bacteria
Quorum sensing  in luminescent bacteriaQuorum sensing  in luminescent bacteria
Quorum sensing in luminescent bacteria
 
Microbial interaction.pptx
Microbial interaction.pptxMicrobial interaction.pptx
Microbial interaction.pptx
 
Thermal Stress and the Heat Shock Response in Microbes
Thermal Stress and the Heat Shock Response in MicrobesThermal Stress and the Heat Shock Response in Microbes
Thermal Stress and the Heat Shock Response in Microbes
 
Sulphur cycle.pptx
Sulphur cycle.pptxSulphur cycle.pptx
Sulphur cycle.pptx
 
Aspergillus niger (FUNGUS)
Aspergillus niger  (FUNGUS)Aspergillus niger  (FUNGUS)
Aspergillus niger (FUNGUS)
 
Myxobacteria, life cycle, genetic basis of differentiation
Myxobacteria, life cycle, genetic basis of differentiationMyxobacteria, life cycle, genetic basis of differentiation
Myxobacteria, life cycle, genetic basis of differentiation
 
Quorum sensing in bacterial populations
Quorum sensing in bacterial populationsQuorum sensing in bacterial populations
Quorum sensing in bacterial populations
 
Primary screening
Primary screeningPrimary screening
Primary screening
 
Isolation of antibiotic resistance mutant by replica plating
Isolation of antibiotic resistance mutant by replica platingIsolation of antibiotic resistance mutant by replica plating
Isolation of antibiotic resistance mutant by replica plating
 
Type iii bacterial secretion system
Type iii bacterial secretion systemType iii bacterial secretion system
Type iii bacterial secretion system
 
Bacillus thurigenesis
Bacillus thurigenesisBacillus thurigenesis
Bacillus thurigenesis
 
Starvation Stress Response (Bacterial)
Starvation Stress Response (Bacterial)Starvation Stress Response (Bacterial)
Starvation Stress Response (Bacterial)
 

Similar to Quorum sensing 2016

Staphylococcus aureus
Staphylococcus aureusStaphylococcus aureus
Staphylococcus aureusuroojali99
 
Pseudomonas dr.ihsan alsaimary
Pseudomonas dr.ihsan alsaimaryPseudomonas dr.ihsan alsaimary
Pseudomonas dr.ihsan alsaimarydr.Ihsan alsaimary
 
Pneumonia Disease Research Paper
Pneumonia Disease Research PaperPneumonia Disease Research Paper
Pneumonia Disease Research PaperHaley Johnson
 
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...SUS GROUP OF INSTITUTIONS
 
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_310 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3ahsanrabbani
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilmsMicrobiology
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilmsMicrobiology
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilmsMicrobiology
 
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & Anthrax
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & AnthraxZoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & Anthrax
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & AnthraxEneutron
 
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseases
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseasesreverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseases
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseasesRaditijo Hamidjaja
 
Enteroviruses life cycle structure genome organization classification
Enteroviruses life cycle structure genome organization classificationEnteroviruses life cycle structure genome organization classification
Enteroviruses life cycle structure genome organization classificationMuhammad Ismail
 
Mycoplasma contamination of cell cultures
Mycoplasma contamination of cell culturesMycoplasma contamination of cell cultures
Mycoplasma contamination of cell culturesindranil chatterjee
 
oral presentation Anmol, Maninder and Parneet.pptx
oral presentation Anmol, Maninder and Parneet.pptxoral presentation Anmol, Maninder and Parneet.pptx
oral presentation Anmol, Maninder and Parneet.pptxAnmoldeepToor1
 
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...Eneutron
 
How Microorganisms talking ?
How Microorganisms talking ?How Microorganisms talking ?
How Microorganisms talking ?Microbiology
 
Microbiology of HIV
Microbiology of HIVMicrobiology of HIV
Microbiology of HIVGAYATHRIM67
 
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...Pig Farm Solution
 
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...Neha Vats
 

Similar to Quorum sensing 2016 (20)

Sulphur cycle.pptx
Sulphur cycle.pptxSulphur cycle.pptx
Sulphur cycle.pptx
 
Staphylococcus aureus
Staphylococcus aureusStaphylococcus aureus
Staphylococcus aureus
 
Pseudomonas dr.ihsan alsaimary
Pseudomonas dr.ihsan alsaimaryPseudomonas dr.ihsan alsaimary
Pseudomonas dr.ihsan alsaimary
 
Pneumonia Disease Research Paper
Pneumonia Disease Research PaperPneumonia Disease Research Paper
Pneumonia Disease Research Paper
 
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...
PREVALENCE AND CHARACTERIZATION OF VIRULENCE PROPERTIES OF PSEUDOMONAS AERUGI...
 
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_310 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3
10 aerobic actinomycetes-and_anaerobic_____actinomyces_v1-_3
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilms
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilms
 
quorum sensing and biofilms
quorum sensing and biofilmsquorum sensing and biofilms
quorum sensing and biofilms
 
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & Anthrax
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & AnthraxZoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & Anthrax
Zoonotic Infections. Bacillus Anthracis, Brucella. Brucellosis & Anthrax
 
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseases
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseasesreverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseases
reverse-line-blot-hybridisation-in-the-detection-of-tick-borne-diseases
 
New era antimicrobials
New era antimicrobialsNew era antimicrobials
New era antimicrobials
 
Enteroviruses life cycle structure genome organization classification
Enteroviruses life cycle structure genome organization classificationEnteroviruses life cycle structure genome organization classification
Enteroviruses life cycle structure genome organization classification
 
Mycoplasma contamination of cell cultures
Mycoplasma contamination of cell culturesMycoplasma contamination of cell cultures
Mycoplasma contamination of cell cultures
 
oral presentation Anmol, Maninder and Parneet.pptx
oral presentation Anmol, Maninder and Parneet.pptxoral presentation Anmol, Maninder and Parneet.pptx
oral presentation Anmol, Maninder and Parneet.pptx
 
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...
Pathogenic Rickettsia. Human epidemic thyphus & Murine Thyphus. Coxiella Burn...
 
How Microorganisms talking ?
How Microorganisms talking ?How Microorganisms talking ?
How Microorganisms talking ?
 
Microbiology of HIV
Microbiology of HIVMicrobiology of HIV
Microbiology of HIV
 
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...
Phage Endolysins as Potential Antimicrobials against Multidrug Resistant Vibr...
 
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...
Quorum Sensing in detection of Pseudomonas aeuroginosa biofilms in cystic fib...
 

Recently uploaded

Digital Dentistry.Digital Dentistryvv.pptx
Digital Dentistry.Digital Dentistryvv.pptxDigital Dentistry.Digital Dentistryvv.pptx
Digital Dentistry.Digital Dentistryvv.pptxMohamedFarag457087
 
Understanding Partial Differential Equations: Types and Solution Methods
Understanding Partial Differential Equations: Types and Solution MethodsUnderstanding Partial Differential Equations: Types and Solution Methods
Understanding Partial Differential Equations: Types and Solution Methodsimroshankoirala
 
FAIRSpectra - Enabling the FAIRification of Analytical Science
FAIRSpectra - Enabling the FAIRification of Analytical ScienceFAIRSpectra - Enabling the FAIRification of Analytical Science
FAIRSpectra - Enabling the FAIRification of Analytical ScienceAlex Henderson
 
Taphonomy and Quality of the Fossil Record
Taphonomy and Quality of the  Fossil RecordTaphonomy and Quality of the  Fossil Record
Taphonomy and Quality of the Fossil RecordSangram Sahoo
 
CYTOGENETIC MAP................ ppt.pptx
CYTOGENETIC MAP................ ppt.pptxCYTOGENETIC MAP................ ppt.pptx
CYTOGENETIC MAP................ ppt.pptxCherry
 
Genome sequencing,shotgun sequencing.pptx
Genome sequencing,shotgun sequencing.pptxGenome sequencing,shotgun sequencing.pptx
Genome sequencing,shotgun sequencing.pptxCherry
 
Lipids: types, structure and important functions.
Lipids: types, structure and important functions.Lipids: types, structure and important functions.
Lipids: types, structure and important functions.Cherry
 
COMPOSTING : types of compost, merits and demerits
COMPOSTING : types of compost, merits and demeritsCOMPOSTING : types of compost, merits and demerits
COMPOSTING : types of compost, merits and demeritsCherry
 
Human genetics..........................pptx
Human genetics..........................pptxHuman genetics..........................pptx
Human genetics..........................pptxCherry
 
POGONATUM : morphology, anatomy, reproduction etc.
POGONATUM : morphology, anatomy, reproduction etc.POGONATUM : morphology, anatomy, reproduction etc.
POGONATUM : morphology, anatomy, reproduction etc.Cherry
 
Dr. E. Muralinath_ Blood indices_clinical aspects
Dr. E. Muralinath_ Blood indices_clinical  aspectsDr. E. Muralinath_ Blood indices_clinical  aspects
Dr. E. Muralinath_ Blood indices_clinical aspectsmuralinath2
 
FAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
FAIRSpectra - Enabling the FAIRification of Spectroscopy and SpectrometryFAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
FAIRSpectra - Enabling the FAIRification of Spectroscopy and SpectrometryAlex Henderson
 
Use of mutants in understanding seedling development.pptx
Use of mutants in understanding seedling development.pptxUse of mutants in understanding seedling development.pptx
Use of mutants in understanding seedling development.pptxRenuJangid3
 
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRings
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRingsTransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRings
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRingsSérgio Sacani
 
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry Areesha Ahmad
 
Porella : features, morphology, anatomy, reproduction etc.
Porella : features, morphology, anatomy, reproduction etc.Porella : features, morphology, anatomy, reproduction etc.
Porella : features, morphology, anatomy, reproduction etc.Cherry
 
PODOCARPUS...........................pptx
PODOCARPUS...........................pptxPODOCARPUS...........................pptx
PODOCARPUS...........................pptxCherry
 
Pteris : features, anatomy, morphology and lifecycle
Pteris : features, anatomy, morphology and lifecyclePteris : features, anatomy, morphology and lifecycle
Pteris : features, anatomy, morphology and lifecycleCherry
 
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIA
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIACURRENT SCENARIO OF POULTRY PRODUCTION IN INDIA
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIADr. TATHAGAT KHOBRAGADE
 
GBSN - Microbiology (Unit 4) Concept of Asepsis
GBSN - Microbiology (Unit 4) Concept of AsepsisGBSN - Microbiology (Unit 4) Concept of Asepsis
GBSN - Microbiology (Unit 4) Concept of AsepsisAreesha Ahmad
 

Recently uploaded (20)

Digital Dentistry.Digital Dentistryvv.pptx
Digital Dentistry.Digital Dentistryvv.pptxDigital Dentistry.Digital Dentistryvv.pptx
Digital Dentistry.Digital Dentistryvv.pptx
 
Understanding Partial Differential Equations: Types and Solution Methods
Understanding Partial Differential Equations: Types and Solution MethodsUnderstanding Partial Differential Equations: Types and Solution Methods
Understanding Partial Differential Equations: Types and Solution Methods
 
FAIRSpectra - Enabling the FAIRification of Analytical Science
FAIRSpectra - Enabling the FAIRification of Analytical ScienceFAIRSpectra - Enabling the FAIRification of Analytical Science
FAIRSpectra - Enabling the FAIRification of Analytical Science
 
Taphonomy and Quality of the Fossil Record
Taphonomy and Quality of the  Fossil RecordTaphonomy and Quality of the  Fossil Record
Taphonomy and Quality of the Fossil Record
 
CYTOGENETIC MAP................ ppt.pptx
CYTOGENETIC MAP................ ppt.pptxCYTOGENETIC MAP................ ppt.pptx
CYTOGENETIC MAP................ ppt.pptx
 
Genome sequencing,shotgun sequencing.pptx
Genome sequencing,shotgun sequencing.pptxGenome sequencing,shotgun sequencing.pptx
Genome sequencing,shotgun sequencing.pptx
 
Lipids: types, structure and important functions.
Lipids: types, structure and important functions.Lipids: types, structure and important functions.
Lipids: types, structure and important functions.
 
COMPOSTING : types of compost, merits and demerits
COMPOSTING : types of compost, merits and demeritsCOMPOSTING : types of compost, merits and demerits
COMPOSTING : types of compost, merits and demerits
 
Human genetics..........................pptx
Human genetics..........................pptxHuman genetics..........................pptx
Human genetics..........................pptx
 
POGONATUM : morphology, anatomy, reproduction etc.
POGONATUM : morphology, anatomy, reproduction etc.POGONATUM : morphology, anatomy, reproduction etc.
POGONATUM : morphology, anatomy, reproduction etc.
 
Dr. E. Muralinath_ Blood indices_clinical aspects
Dr. E. Muralinath_ Blood indices_clinical  aspectsDr. E. Muralinath_ Blood indices_clinical  aspects
Dr. E. Muralinath_ Blood indices_clinical aspects
 
FAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
FAIRSpectra - Enabling the FAIRification of Spectroscopy and SpectrometryFAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
FAIRSpectra - Enabling the FAIRification of Spectroscopy and Spectrometry
 
Use of mutants in understanding seedling development.pptx
Use of mutants in understanding seedling development.pptxUse of mutants in understanding seedling development.pptx
Use of mutants in understanding seedling development.pptx
 
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRings
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRingsTransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRings
TransientOffsetin14CAftertheCarringtonEventRecordedbyPolarTreeRings
 
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
GBSN - Biochemistry (Unit 2) Basic concept of organic chemistry
 
Porella : features, morphology, anatomy, reproduction etc.
Porella : features, morphology, anatomy, reproduction etc.Porella : features, morphology, anatomy, reproduction etc.
Porella : features, morphology, anatomy, reproduction etc.
 
PODOCARPUS...........................pptx
PODOCARPUS...........................pptxPODOCARPUS...........................pptx
PODOCARPUS...........................pptx
 
Pteris : features, anatomy, morphology and lifecycle
Pteris : features, anatomy, morphology and lifecyclePteris : features, anatomy, morphology and lifecycle
Pteris : features, anatomy, morphology and lifecycle
 
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIA
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIACURRENT SCENARIO OF POULTRY PRODUCTION IN INDIA
CURRENT SCENARIO OF POULTRY PRODUCTION IN INDIA
 
GBSN - Microbiology (Unit 4) Concept of Asepsis
GBSN - Microbiology (Unit 4) Concept of AsepsisGBSN - Microbiology (Unit 4) Concept of Asepsis
GBSN - Microbiology (Unit 4) Concept of Asepsis
 

Quorum sensing 2016

  • 1. Molecular Basis of Quorum Sensing in Virulence of Bacterial Pathogens Tuesday, May 31, 2016 1 Shezaib Siddiqui Research Fellow
  • 2.  Introduction  What is Quorum Sensing?  Molecular basis of infections a. Staphylococcus aureus b. Pseudomonas aeruginosa  Biosynthesis and degradation of Quorum sensing  Therapeutic approaches 2
  • 3. 3
  • 4. KEY TERMS Pathogenicity: The ability of an organism to cause a disease. Virulence: The degree of pathogenicity or disease caused by a pathogen. OR Total no. of pathogenic determinants an organism is collectively termed as virulence. 4
  • 5.  Phenomenon that regulates the gene expression of bacterial population in unison at particular density in response to secreted chemical molecules. OR  Synchronous gene expression of bacterial population in an environment. 5
  • 6. HISTORY o First Identified in late1960s by Nealson et al. o Discovered in Vibrio fischeri and Vibrio harveyii o V. fischeri is a symbiotic microbiota of Howaiian bobtail squid light organ. o V. Harveyi is a free living marine bacterium o Bioluminescence in Vibrio is control via Quorum sensing (QS). o Lux operon was discovered as QS regulatory coding region. 6 Howaiin bobtail squid Vibrio fischerii Vibrio harveyi
  • 7. Quorum Sensing in a Nut Shell Production and release of signalling molecule (Auto inducer). Diffusion of Auto inducer (AI) molecule at low cell density leaving the QS circuit in-active Activation of QS circuit by AI at higher concentration due to Higher cell density. Transcriptional activation of down regulating genes by AI receptor complex or other activated signalling molecule. Activation of virulence, biofilm formation, sporulation, competence and antibiotic production. 7
  • 8. QS IN GRAM NEGATIVE BACTERIA  The autoinducers are typically molecules called acyl- homoserine lactones (AHLs).  AHLs diffuses extracellular and intracellular via passive transport. QS IN GRAM POSITIVE BACTERIA  The autoinducers are oligopeptides, short peptides typically 8-10 amino acids long.  Oligopeptides excretes in extracellular environment via active transport. 8
  • 9. Schematic Representation of QS Circuits Canonical bacterial quorum-sensing (QS) circuits. Autoinducing peptide (AIP) QS in Gram- positive bacteria by (A) two-component signalling, or (B) an AIP-binding transcription factor. Small molecule QS in Gram-negative bacteria by (C) a LuxI/LuxR-type system, or (D) two- component signalling. Gram positive Gram negative
  • 10. QS Circuit of Vibrio harveyi Lux Bioluminescence System
  • 11. 11
  • 12. 12
  • 13.  S. aureus is a gram positive opportunistic pathogen.  Causative agent of many cumbersome respiratory and skin infections and poisonings.  Few of high mortality infections and poisonings are Scalded skin syndrome, toxic shock syndrome, furuncles, carbuncles, sinusitis, otitis media etc.  Emerged as Multi drug resistant bug and many hospital setting.  Prevalent in > 60% of Nosocomial infections  MRSA has mortality rate of >20% 13
  • 14.  Encode various virulence factor under the control of Quorum sensing system (Agr operon) 14 Scalded Skin Syndrome Impetigo Toxic shock syndrome Otitis media
  • 15.  S. aureus has a peptide based quorum sensing system ,encoded by accessory gene regulator (agr) locus.  The agr locus controls transcription of two RNA transcripts RNA II and RNA III from promoter P2 and P3, respectively.  RNA II encodes Agr A, B, C and D proteins  RNA III encodes δ-hemolysin and posses regulatory activity. 15 Protein Function Agr A Transcription factor (Activated by Agr C) Agr B Triming and transport of pre- AIP (Agr D) Agr C Histidine Kinase recetor of AIP Agr D Pre- Auto inducer peptide Table 1: components of agr system
  • 16. The Agr System 16 QS Circuit of Staphylococcus aureus
  • 17. Role of RNAIII in virulence:  5’ end upregulates transcription of α- hemolysin.  3’ end is responsible for the repression of rot (repressor of toxin) protein and Protein A.  Rot inhibits the transcription of various toxins.  Inhibition of rot upregulates the translation of toxins and increases virulence.  Repression of Protein A (cell surface protein) decease adhesion of biofilm. 17
  • 18. Role of Agr in Biofilm control:  Agr A up regulates the translation of PSMs (Phenol soluble modulins).  PSMs are peptide toxin that help in channel formation in tissues.  PSMs also acts as surfactants that allow biofilm dispersal.  Biofilm dispersal helps S. aureus to colonize and infect new sites. 18
  • 19. Polymorphism in Agr Locus  S. aureus can be classified in to 4 distinct groups based on Agr locus. 19 Agr locus Agr I Agr II Agr III Agr IV
  • 21.  P.aeruginosa is a Gram-negative opportunistic pathogen.  Responsible for severe nosocomial infections cellulitis, UTIs, endocarditis and epidermidis bullosa.  Accounts for more than 10% of nosocomial infections.  Patients with Cystic Fibrosis, injuries (especially burns/boils) are highly susceptible to P. aeruginosa infections.  Second leading cause of ventilator associated pneumonia.  Difficult to treat due to emerging drug resistance. 21
  • 23. 23 • Three QS circuits are identified • LasI/R (3-0C12HL synthase/ Receptor) • RhlI/R (C4HL synthase/ Receptor) • Pseudomonas Quinolone Signal (PQS) Las Inducer/Repressor (I/R) system: • Auto-induced by LasI • Controls RhlR operon • Activates transcription of Las B (Elastase), LasA (Protease), tox A (Exotoxin A) and aprA (alkaline phosphatase). • LasI inhibits Rhl R.
  • 24. RhlI/R system:  Upregulates rhl I ◦  Positive regulator of Las B (elastase), RhlA and B (Rhamnosyl transferase), RpoS (Stationary phase σ factor) and Pyocanin (niche molecule) 24
  • 25. 25
  • 26.  Negative regulation NFκB.  Induces apoptosis in macrophages.  Down regulates TNF-α and IL-12.  Induces IL-8 from human bronchial epithelial cells. 26
  • 27. Biosynthesis and degradation of Acyl Homo serine Lactones 27 Fatty acid pathway AHL synthase
  • 28. 28 Types of Auto inducers in gram negative bacteria PAME= propionyl amphotericin B methyl ester, DSF= Diffusible signal factor, THMF= tetra hydroxyl methyl furan
  • 29. 29
  • 30.  Novel therapeutic tartest against multi drug resistant bacteria.  Reported to decrease virulence only, thus empower host immune system to combat attenuated pathogen.  Low chances of drug resistance against quorum quenchers as they do not kill bacteria. 30
  • 31. Strategies for Quroum Sensing Inhibition 1. Elimination of signal  By stimulating enzymatic degradation of auto inducer  By inhibition of auto inducer biosynthesis and receptor molecule biosynthesis 2. Inhibition of signal receptor complex  By using auto inducer analogues  By treating with antibodies against auto inducer 31
  • 32. Current Approaches for QS inhibition  AHL acylases, paraxonases and AHL lactonases are secreted by many bacteria to degrade AHL , therefore negatively control QS.  AHL and AIP analogues have been synthesized to inhibits QS in S. aureus, P. aeruginosa and other pathogens  Synthesis of inhibitor molecules against enzymes involved in AHL biosynthesis, eg: tricolsan inhibits enoyl-ACP reductase.  Inhibition of auto inducer receptors by using RNAi technology. 32
  • 33. 33
  • 34. 34 Auto Inducer and Inhibitors of P. aeruginosa
  • 35. 35 Auto inducers and analogue Inhibitors of S. aureus s
  • 36.  QS circuits serve as new and potential anti virulence target to control infections with reduces risks of resistance evolution. 36
  • 37.  Miller, Melissa B., and Bonnie L. Bassler. "Quorum sensing in bacteria."Annual Reviews in Microbiology 55.1 (2001): 165-199.  Waters, Christopher M., and Bonnie L. Bassler. "Quorum sensing: cell-to- cell communication in bacteria." Annu. Rev. Cell Dev. Biol. 21 (2005): 319-346.  Whiteley, Marvin, Kimberly M. Lee, and E. P. Greenberg. "Identification of genes controlled by quorum sensing in Pseudomonas aeruginosa."Proceedings of the National Academy of Sciences 96.24 (1999): 13904-13909.  Bassler, Bonnie L. "How bacteria talk to each other: regulation of gene expression by quorum sensing." Current opinion in microbiology 2.6 (1999): 582-587.  Yarwood, Jeremy M., et al. "Quorum sensing in Staphylococcus aureus biofilms." Journal of bacteriology 186.6 (2004): 1838-1850.  Rutherford, Steven T., and Bonnie L. Bassler. "Bacterial quorum sensing: its role in virulence and possibilities for its control." Cold Spring Harbor Perspectives in Medicine 2.11 (2012): a012427. 37
  • 38. 38

Editor's Notes

  1. Canonical bacterial quorum-sensing (QS) circuits. Autoinducing peptide (AIP) QS in Gram-positive bacteria by (A) two-component signaling, or (B) an AIP-binding transcription factor. Small molecule QS in Gram-negative bacteria by (C) a LuxI/LuxR-type system, or (D) two-component signaling.
  2. In P.aeruginosa at least three interwined quorum sensing (QS) system and one orphan autoinducer receptor affect the ability of this organism to cause disease.