Mechanism and Function of Actin Pedestal Formation by Enterohemorrhagic <em>Escherichia coli</em> O157:H7: A Dissertation
AuthorsBrady, Michael John
Faculty AdvisorPeter Pryciak, Ph.D.
Academic ProgramMolecular Genetics and Microbiology
UMass Chan AffiliationsBiochemistry and Molecular Pharmacology
Document TypeDoctoral Dissertation
KeywordsEscherichia coli O157
Escherichia coli Proteins
Amino Acids, Peptides, and Proteins
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AbstractEnterohemorrhagic Escherichia coli O157:H7 (EHEC) and enteropathogenic E. coli O127:H7 (EPEC) induce characteristic F-actin rich pedestals on infected mammalian cells. Each pathogen delivers its own translocated intimin receptor (Tir) to the host cell to act as a receptor for the bacterial outer membrane adhesin, intimin. Interaction of translocated Tir with intimin is essential for mammalian cell binding and host colonization, as well as to induce actin pedestal formation in vitro. In spite of these parallels, EHEC and EPEC Tir appear to generate actin pedestals by distinct mechanisms. Further, while the ability to form actin pedestals is a striking phenotype, the function of pedestals during infection remains unclear. To address these issues, a systematic and quantitative analysis of Tir-mediated actin assembly was conducted. We identified a three-residue Tir sequence involved in actin pedestal formation for both EHEC and EPEC, and developed evidence that the two pathogens trigger a common pathway for actin assembly. Further, the ability of these bacteria to promote actin assembly appears to promote both intimin-mediated bacterial binding in vitro and optimal colonization during experimental animal infection.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/31660
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