Enterobacterial factors antagonize host defense

Stable Identifier
R-HSA-9956593
DOI
10.3180/R-HSA-9956593.2
Type
Pathway
Species
Homo sapiens
Related Species
Shigella flexneri, Escherichia coli O157:H7
Compartment
cytosol
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Enterobacterial factors antagonize host defense
Click the image above or here to open this pathway in the Pathway Browser
This Reactome event describes mechanisms used by intracellular bacterial pathogens that deploy type III secretion system (T3SS) effectors to inhibit caspase-4 (CASP4)-mediated pyroptosis, a lytic form of cell death triggered during infection. Specifically, Shigella flexneri secretes OspC3, which catalyzes ADP-riboxanation of CASP4, thereby inhibiting its catalytic activity and blocking lipopolysaccharide (LPS)-induced pyroptosis (Kobayashi T et al., 2013; Li Z et al., 2021; Hou Y et al., 2023). Pathogenic Escherichia coli strains secrete the T3SS effector NleF, which directly binds and inhibits CASP4 as well as apoptotic caspases CASP8 and CASP9 (Blasche S et al., 2013). The crystal structure of the NleF:CASP9 complex revealed a novel inhibitory mechanism involving insertion of the NleF carboxy-terminus into the protease active site (Blasche S et al., 2013). Bacterial NleF blocks CASP4 activation in vitro and also inhibits CASP4 during enteropathogenic (EPEC) or enterohemorrhagic (EHEC) infection in epithelial cells (Pallett MA et al., 2017; Song T et al., 2017). During EPEC infection, NleF suppresses CASP4 activity and CASP4-dependent interleukin-18 (IL-18) processing (Pallett MA et al., 2017).
Literature References
PubMed ID Title Journal Year
23516580 The E. coli effector protein NleF is a caspase inhibitor

Blasche, S, Mörtl, M, Steuber, H, Siszler, G, Nisa, S, Schwarz, F, Lavrik, I, Gronewold, TM, Maskos, K, Donnenberg, MS, Ullmann, D, Uetz, P, Kögl, M

PLoS One 2013
27624779 Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells

Pallett, MA, Crepin, VF, Serafini, N, Habibzay, M, Kotik, O, Sanchez-Garrido, J, Di Santo, JP, Shenoy, AR, Berger, CN, Frankel, G

Mucosal Immunol 2017
36624349 Structural mechanisms of calmodulin activation of Shigella effector OspC3 to ADP-riboxanate caspase-4/11 and block pyroptosis

Hou, Y, Zeng, H, Li, Z, Feng, N, Meng, F, Xu, Y, Li, L, Shao, F, Ding, J

Nat Struct Mol Biol 2023
23684308 The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection

Kobayashi, T, Ogawa, M, Sanada, T, Mimuro, H, Kim, M, Ashida, H, Akakura, R, Yoshida, M, Kawalec, M, Reichhart, JM, Mizushima, T, Sasakawa, C

Cell Host Microbe 2013
Participants
Events
Participates
as an event of
Disease
Name Identifier Synonyms
disease by infectious agent DOID:0050117 infectious disease
Cross References
Mondo
Authored
Shamovsky, V  (2025-06-10)
Reviewed
Shi, X  (2025-08-12)
Matthews, L  (2025-11-03)
Created
Shamovsky, V  (2025-06-13)
Cite Us!