Metalloprotease type III effectors that specifically cleave JNK and NF-κB.
Two major arms of the inflammatory response are the NF-κB and c-Jun N-terminal kinase (JNK) pathways. Here, we show that enteropathogenic Escherichia coli (EPEC) employs the type III secretion system to target these two signalling arms by injecting host cells with two effector proteins, NleC and NleD. We provide evidence that NleC and NleD are Zn-dependent endopeptidases that specifically clip and inactivate RelA (p65) and JNK, respectively, thus blocking NF-κB and AP-1 activation. We show that NleC and NleD co-operate and complement other EPEC effectors in accomplishing maximal inhibition of IL-8 secretion. This is a remarkable example of a pathogen using multiple effectors to manipulate systematically the host inflammatory response signalling network.
Department of Microbiology and Molecular Genetics, IMRIC, The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel.
Kobi
K
Baruch
Lihi
L
Gur-Arie
Chen
C
Nadler
Simi
S
Koby
Gal
G
Yerushalmi
Yinon
Y
Ben-Neriah
Orli
O
Yogev
Eitan
E
Shaulian
Chen
C
Guttman
Raz
R
Zarivach
Ilan
I
Rosenshine
D017209:Apoptosis; D054308:Enteropathogenic Escherichia coli / Q000276:immunology / Q000502:physiology*; D004927:Escherichia coli Infections / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D048031:JNK Mitogen-Activated Protein Kinases / Q000276:immunology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology*; D051996:Transcription Factor RelA / Q000276:immunology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D029968:Escherichia coli Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C506688:Z0986 protein, E coli; C506689:Z0990 protein, E coli; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases