Cutting edge: Salmonella AvrA effector inhibits the key proinflammatory, anti-apoptotic NF-kappa B pathway.
Secreted prokaryotic effector proteins have evolved to modulate the cellular functions of specific eukaryotic hosts. Generally, these proteins are considered virulence factors that facilitate parasitism. However, in certain plant and insect eukaryotic/prokaryotic relationships, effector proteins are involved in the establishment of commensal or symbiotic interactions. In this study, we report that the AvrA protein from Salmonella typhimurium, a common enteropathogen of humans, is an effector molecule that inhibits activation of the key proinflammatory NF-kappaB transcription factor and augments apoptosis in human epithelial cells. This activity is similar but mechanistically distinct from that described for YopJ, an AvrA homolog expressed by the bacterial pathogen Yersinia. We suggest that AvrA may limit virulence in vertebrates in a manner analogous to avirulence factors in plants, and as such, is the first bacterial effector from a mammalian pathogen that has been ascribed such a function.
Collier-Hyams
Lauren S
LS
Epithelial Pathobiology Unit, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Zeng
Hui
H
Sun
Jun
J
Tomlinson
Amelia D
AD
Bao
Zhao Qin
ZQ
Chen
Huaqun
H
Madara
James L
JL
Orth
Kim
K
Neish
Andrew S
AS
D017209:Apoptosis / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010766:Phosphorylation; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*
C405989:AvrA protein, Salmonella dublin; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007166:Immunosuppressive Agents; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C109227:YopP protein, Yersinia; D000072000:NF-KappaB Inhibitor alpha