How Do the Virulence Factors of Shigella Work Together to Cause Disease?
The complex host-pathogen interplay involves the recognition of the pathogen by the host’s innate immune system and countermeasures taken by the pathogen. Detection of invading bacteria by the host leads to rapid activation of the transcription factor NF-kB, followed by inflammation and eradication of the intruders. In response, some pathogens, including enteropathogenic Escherichia coli (EPEC), acquired means of blocking NF-kB activation. We show that inhibition of NF-kB activation by EPEC involves the injection of NleE into the host cell. Importantly, we show that NleE inhibits NF-kB activation by preventing activation of IKKb and consequently the degradation of the NF-kB inhibitor, IkB. This NleE activity is enhanced by, but is not dependent on, a second injected effector, NleB. In conclusion, this study describes two effectors, NleB and NleE, with no similarity to other known proteins, used by pathogens to manipulate NF-kB signaling pathways. Citation: Nadler C, Baruch K, Kobi S, Mills E, Haviv G, et al. (2010) The Type III Secretion Effector NleE Inhibits NF-kB Activation. PLoS Pathog 6(1): e1000743. doi:10.1371/journal.ppat.1000743 Editor: David S. Schneider, Stanford University, United States of America Received May 19, 2009; Accepted December 29, 2009; Published January 29, 2010 Copyright: 2010 Nadler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was supported by grants from the Chief Scientist Office of the Ministry of Health, Israel (to IR), the German Israel Binational Foundation (GIF, to TFM, IR, and YBN), and the EraNet Pathogenomic program (IR and TFM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: email@example.com