Shiga Toxins Intracellular Trafficking to the ER Leading to Activation of Host Cell Stress Responses 英文参考文献.docVIP

Toxins 2010, 2, 1515-1535; doi:10.3390/toxins2061515 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Shiga Toxins: Intracellular Trafficking to the ER Leading to Activation of Host Cell Stress Responses Moo-Seung Lee, Rama P. Cherla and Vernon L. Tesh * Department of Microbial and Molecular Pathogenesis, Texas A M Health Science Center, 407 Joe H. Reynolds Medical Building, College Station, TX, 77843-1114, USA; E-Mails: mlee@ (M.-S.L.); rpcherla@ (R.P.C) * Author to whom correspondence should be addressed; E-Mail: tesh@; Tel.: +1-979-845-1314; Fax: +1-979-845-3479. Received: 27 April 2010; in revised form: 18 May 2010 / Accepted: 1 June 2010 / Published: 17 June 2010 Abstract: Despite efforts to improve hygenic conditions and regulate food and drinking water safety, the enteric pathogens, Shiga toxin-producing Escherichia coli (STEC) and Shigella dysenteriae serotype 1 remain major public health concerns due to widespread outbreaks and the severity of extra-intestinal diseases they cause, including acute renal failure and central nervous system complications. Shiga toxins are the key virulence factors expressed by these pathogens mediating extra-intestinal disease. Delivery of the toxins to the endoplasmic reticulum (ER) results in host cell protein synthesis inhibition, activation of the ribotoxic stress response, the ER stress response, and in some cases, the induction of apoptosis. Intrinsic and/or extrinsic apoptosis inducing pathways are involved in executing cell death following intoxication. In this review we provide an overview of the current understanding Shiga toxin intracellular trafficking, host cellular responses to the toxin and ER stress-induced apoptosis with an emphasis on recent findings. Keywords: Shiga toxins; retrograde transport; ribotoxic stress response; ER stress response; apoptosis  Toxins 2010, 2 1516 1. Introduction Shiga toxins (alternatively called verotox