Molecular Genetics and Microbiology, The Hebrew University of Jerusalem, Jerusalem
Enteropathogenic Escherichia coli (EPEC) bacteria are etiological agents of human diarrhea, and remain a significant cause of infant mortality in developing countries. As many other pathogenic bacteria, EPEC possess a syringe-like organelle termed type III secretion system (TTSS), which serves to inject toxic proteins (effectors) into gut epithelial cells. The injected effectors target different host-cell processes to subvert host signaling networks and allow efficient host colonization. Twenty one effector encoding genes have been described for EPEC, among them is nleD. Previously we showed that NleD is a zinc dependent endopeptidase that specifically cleaves the eukaryotic Mitogen-activated protein kinases (MAPKs) JNK and p38, but not ERK. We showed that NleD cleaves MAPKs in the activation loop after the x within the TxY motif, and subsequently inactivates them. Computational analysis reveals several orthologs to nleD from other bacterial species, suggesting that MAPKs are common targets to pathogens. Currently we are investigating the structural mechanism for MAPKs cleavage by nleD and the basis for the specificity.