Art of Bacterial warfare.1ppt

Art of Bacterial warfare : 

Art of Bacterial warfare Dr. Anand

Bacteria – Friends / Foes !!?? : 

Bacteria – Friends / Foes !!?? 100 1000

Strange.. But true! : 

Strange.. But true! Who’s strong! A war.. Microbes have always had the upper hand .. Odd that we know the organisms for decades/ centuries ..but .. Not quite! Where have we missed to understand them???

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Art of Bacterial warfare MICROBIOTERRORISM Many pathogens.. Many strategies .. yet aim is same…. Cause disease!!

Bacterial attack strategies.. Multifaceted.. : 

Bacterial attack strategies.. Multifaceted.. Contact with susceptible host Adhesion Invasion Local spread Dissemination and distant spread Evasion of immune system Cell death DISEASE Part we virtually ignored

Bacterial secretion systems : 

Bacterial secretion systems Highly specialized devices for delivery of effectors weapon of Gram –ve pathogens Single bacterium possess either one type or combination with another (Bacterial guns!!)

Bacterial adhesion : 

Bacterial adhesion Crucial - Establishes firm contact Tools for adhesion Pili & fimbria Adhesins Fibronectin binding proteins

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Pili and Fimbria filamentous surface structures, a scaffold-like rod anchored to bacterial outer membrane Species specific and diverse Morphologically 6 types described Adhesin at the tip of the scaffold, confers binding specificity Significance!!? Pilicides- bicyclic 2- pyridones

NOVEL STRATEGIES FOR BACTERIAL ADHESION : 

NOVEL STRATEGIES FOR BACTERIAL ADHESION

H. Pylori - master of many tricks! : 

H. Pylori - master of many tricks! a spiral-shaped gram-negative rod. associated with antral gastritis, duodenal (peptic) ulcer disease, gastric ulcers, and gastric carcinoma. Ability to survive even in most adverse conditions. Pathogenesis- complex

E. Coli- Self Help is the Best Help!! : 

E. Coli- Self Help is the Best Help!! Gram –ve enteric commensal Six pathovars — enteropathogenic E. coli (EPEC), enterohaemorrhagic E. coli (EHEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC; including Shigella), enteroaggregative E. coli (EAEC) and diffusely adherent E. coli (DAEC) — are diarrhoeagenic uropathogenic E. coli (UPEC) and neonatal meningitis E. coli (NMEC) — most common ExPEC isolates

Bacterial encoded receptor : 

Bacterial encoded receptor Probably the most ingenious technique of adhesion An original bacterial adhesion system - the bacteria provides both the ligand and the receptor Described only in EPEC & EHEC till date- Tir/intimin receptor system Process of effectors delivery – includes another amazing delivery tool – Type III secretion system

Tir / Intimin receptor system : 

Tir / Intimin receptor system EPEC and EHEC induce a characteristic lesion, ‘‘attaching and effacing’’ (A/E) phenotype Molecules for the induction of A/E lesions are encoded in a region, the locus of enterocyte effacement (LEE), which codes for a type III secretion system (TTSS) TTSS gene cluster codes for proteins of secretion system as well as effectors to be delivered

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TTSS Tir / Intimin receptor complex

E. Coli rules from THRONE!! : 

E. Coli rules from THRONE!! EPEC & EHEC – Tir/ Intimin receptor system signals downstream pathways – polymerizing actin filaments Result in pedestals formation in host cell plasma membrane Pedestals central to E.coli pathogenesis but precise purpose not known

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Pedestals can surf across membrane Esp F – E.coli secreted protein F Nck – Non catalytic domain kinase N-WASP – Wiskott Aldrich Syndrome protein Arp – Actin related protein Fyn- Src family tyrosine-protein kinase

INVASION : 

Salmonella: Gram –ve ; enterobacteriaceae family ≥ 2500 serotypes known; classification complex Causes typhoid fever, septicaemia, enterocolitis Shigella: Gram –ve ; enterobacteriaceae family Pathogenic species: S dysenteriae , S flexneri ,S boydii, S sonnei Illness limited to gastrointestinal tract Listeria: L monocytogenes -short, gram-positive rod. Meningitis; bactericemia; granulomatous lesions INVASION

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Sip- Salmonella invasion protein Sop- Salmonella outer protein SptP – Salmonella typhimurium protein tyrosine phosphatase Ipa – Invasion plasmid antigen Ipg – Invasion plasmid gene

CELL TO CELL MOTILITY AND LOCAL SPREAD : 

CELL TO CELL MOTILITY AND LOCAL SPREAD Once inside the cell – Shigella effector VirG – Polymerizes actin filaments behind advancing bacterium Aids propulsion of organism and entry into neighboring cell

Molecular mechanism : 

Molecular mechanism

DISSEMINATION AND DISTANT SPREADSafari Ride  : 

DISSEMINATION AND DISTANT SPREADSafari Ride  Pathogenic trick displayed by Salmonella, Yersinia and Legionella Salmonella and Legionella - following ingestion by phagocytes- modify the phagosome into a safe haven Proliferate within phagocytes; disseminate Yersinia – paralyze phagocytes

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LEGIONELLA: Flagellated gram –ve bacilli Shot to fame in 1976!! Causes pneumonia, Pontiac fever

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LEGIONELLA – Outwitting the guards!!! L. pneumophila – acquired by inhalation Peculiarity of able to survive within phagocytes Utilizes T4SS – Dot/Icm system Manipulates the cell, recruits organellar components Generates a replicative niche ( probably the safest place)  Dot/Icm – Defective organelle trafficking / Intracellular multiplication

Molecular mechanism : 

Molecular mechanism SidM SidM – substrate of Icm/Dot transporter LidA – Legionella Icm/Dot protein ARF – ADP ribosylation Factor GDI – Guanine nucleotide Dissociation Inhibitor

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Yersinia gram –ve rod 3 species pathogenic for humans, Y. pestis, Y. enterocolitica,and Y. pseudotuberculosis

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BACTERIAL COMMUNICATION HUMANS are social Animals……….. BACTERIA are… SOCIAL CELLS  QUORUM SENSING Bacterial language!!

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Cell to cell communication process- bacteria produce and detect AUTOINDUCERS- to monitor cell population density & make synchronous response PREPARING FOR BATTLE!!!

DECEIVING HOST DEFENSE SYSTEM : 

DECEIVING HOST DEFENSE SYSTEM

INNATE IMMUNITY & NF-κB PATHWAY : 

INNATE IMMUNITY & NF-κB PATHWAY Tools for tackling: Yersinia spp. – Yop P/J S. Flexneri – OspF & OspG

STRATEGIES FOR ADAPTIVE IMMUNITY : 

STRATEGIES FOR ADAPTIVE IMMUNITY Destroys antibodies ↓ pathogen internalization by APCs Impairs antigen processing , decreases antigen expression Induces apoptosis of APCs

HANDLING HUMORAL IMMUNITY : 

HANDLING HUMORAL IMMUNITY Mucosal surfaces – lined with IgA antibodies , offer protection against pathogen binding N. meningitidis – possess IgA protease – destroys IgA Central to its pathogenesis

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Suppressing Cell’s cry for HELP!!

KILLING STRATEGIES : 

KILLING STRATEGIES Pathogens – induce apoptosis of APCs Mechanism – NF κB dependent pathway e.g Yersinia - Caspase 1 mediated pathway e.g Salmonella pathogen

OUR COUNTERWEAPONS! : 

OUR COUNTERWEAPONS!

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RNA III Inhibiting peptide MIC Bicyclic 2- pyridones

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Thank you!! Gud day!