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About the Authors:
Heather Piscatelli
Affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
Shalaka A. Kotkar
Affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
Megan E. McBee
Current address: Department of Pathology, The University of Chicago, Chicago, Illinois, United States of America
Affiliation: Department of Biological Engineering and Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
Sureshkumar Muthupalani
Affiliation: Department of Biological Engineering and Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
David B. Schauer
Affiliation: Department of Biological Engineering and Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
Robert E. Mandrell
Affiliation: Agricultural Research Service, United States Department of Agriculture, Albany, California, United States of America
John M. Leong
Affiliation: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America
Daoguo Zhou
* E-mail: [email protected]
Affiliation: Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America
Introduction
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important cause of food- and water-borne illnesses in developed countries and in the world. EHEC O157:H7 infections cause hemorrhagic colitis and can result in potentially fatal hemolytic uremia syndrome [1], [2], [3]. EHEC along with Enteropathogenic E. coli (EPEC) and Citrobacter rodentium form a group of pathogens called A/E pathogens that are able to colonize the intestinal mucosa and produce characteristic ‘attaching and effacing’ (A/E) lesions. A/E lesions are characterized by effacement of the brush border microvilli, intimate attachment of the bacterium to the plasma membrane of the enterocytes, and the formation of actin-rich pedestals within the host cell beneath the adherent bacteria [4], [5], [6], [7]. Pedestal formation requires virulence-related EHEC proteins to be injected directly into the host cell through a type III secretion system (TTSS) [8]. Two EHEC O157:H7 type III secreted effectors, Tir and EspFu/TccP, are known to be required for pedestal formation [9], [10], [11]. EspM was shown to inhibit pedestal formation via an unknown mechanism [12], [13].
Tir is a bacteria-made receptor that binds bacterial surface protein intimin to facilitate the pedestal formation [14], [15], [16]. Binding to intimin is followed by coordinated events that lead to rearrangement and/or assembly...