Insertion of E.coli type III secretion system proteins into host cell plasma membrane

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Enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli are Gram negative pathogens that are responsible for a wide spectrum of water borne and food borne infectious diseases. These pathogens are typically associated with severe diarrheal episodes and more rarely in more death, as in the cases observed in the Walkerton, ON outbreak in 2000. EHEC and EPEC have evolved specialized molecular machines called the type III secretions system (TTSS), more commonly known as the molecular needle. The TTSS is a highly efficient molecular structure designed to inject proteins from bacteria directly into the cytoplasmic compartment of epithelial target cells that form the lining of the small intestine. TTSS consists of two groups of proteins called; i) translocators that function to punch a hole in membrane and attaching bacteria to the host cell and ii) effectors which when inject into the host cell trigger marked structural changes that make the intestine leaky and facilitate invasion by bacteria. The objective of this work is to understand how EHEC and EPEC bacteria penetrate the host cell membrane and become anchored. The long term goal of these studies is to understand this process at the molecular level with the aim of using this knowledge to develop strategies for treatment or elimination of infections caused by these food and water bone bacteria.