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Mechanisms of TIII Secretion-Induced Cytotoxicity in Pathogenic Bacteria

Explore the cellular pathways and signaling involved in cell death processes triggered by TIII secretion in bacteria like Shigella, Salmonella, and Yersinia, impacting inflammation, apoptosis, and survival signaling.

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Mechanisms of TIII Secretion-Induced Cytotoxicity in Pathogenic Bacteria

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  1. ANTHRAX

  2. Stimulus Activator MKKK MKK TRAF2 MAPK MEKK1, NIK Targets IKKb IkB NFkB LT = PA + LF ET = PA + EF TRAF6 TAK1 MKK3,6 EF LF p38 Zinc metalloprotease Targets

  3. TRAF2 Pro-inflammatory caspases 1 ,11 FasL TNF Death-receptor Mediated Apoptosis Fas/ CD95 TNFR DISC RIP TRADD FADD DAXX FADD Caspase 8/10 Initiator caspases 2, 8, 9,10 Caspase 8/10 DNA damage Cellular stress IKK Bid IkB NFkB Cyt C IAP Bcl-2 Apaf1 Caspase 9 Executioner caspases 3, 6, 7 Caspase 3 Caspase 6 Caspase 7 ICAD CAD PARP Lamin A Actin Fodrin DNA fragmentation DNA repair Cell shrinkage/membrane blebbing

  4. 2 1 Mechanisms of TIII secretion-induced cytotoxicity: Shigella, Salmonella, and Yersinia CD14 LPS Shigella TLR4 Yersinia Inflammation PMN’s IpaB Caspase 8 IKK (SipB-S.t.) IL-18 IL-1b Caspase 1 NF-kB Survival signals Inflammatory cyt. prod. Apoptosis Cell Death “Pyroptosis” Inflammatory apoptosis macrophage or macrophage-like cell

  5. 2 1 Immunologically silent Mechanisms of TIII secretion-induced cytotoxicity: Shigella, Salmonella, and Yersinia CD14 LPS Shigella TLR4 Yersinia Inflammation PMN’s IpaB Caspase 8 YopJ IKK (SipB-S.t.) IL-18 IL-1b Caspase 1 NF-kB Survival signals Inflammatory cyt. prod. Apoptosis Cell Death “Pyroptosis” Inflammatory apoptosis macrophage or macrophage-like cell

  6. NECROSIS vs. APOPTOSIS LPS, Hoechst (necrosis + apoptosis) LPS, TUNEL (apoptosis) No LPS, Hoechst No LPS, TUNEL 2 3 4 1

  7. Hoechst Annexin V DIC

  8. LPS

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