Molecular Mechanisms Underlying Adhesion and Regulation of Virulence of Human Enterotoxigenic Escherichia coli

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Sakellaris, Harry
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Korolik, Victoria
Ulett, Glen
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2016
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Abstract

Enterotoxigenic Escherichia coli (ETEC) is the key etiological agent of traveller's diarrhea. It accounts for 200 million cases of diarrhea and 380,000 deaths annually. ETEC uses proteinaceous appendages called pili in order to attach with host intestine, followed by secretion of enterotoxins leading to profuse diarrhea. Among various ETEC pili that are characterised till date, CFA/I is the archetype of a class of pili called class 5 ([alpha] pili) pili. CFA/I is composed of two types of protein subunits. It consists of a cylindrical stalk of CfaB subunits and CfaE at the tip. Both intra and inter subunit bonding takes place via donor strand complementation. CfaE is widely accepted as an adhesin molecule that binds to human intestine and human erythrocytes. Also CfaE is regarded as nucleating molecule for pili synthesis (Li et al., 2007, Baker et al., 2009). An AraC family of transcriptional activator (AFTR), Rns is known to regulate CFA/I synthesis and another half of known ETEC pili. Present study focuses on three aspects of ETEC virulence. First, Although CfaE is considered to be the key adhesin, an existing hypothesis claims that CfaB could independently bind to glycosphingolipid receptors, including asialo-GM1. Furthermore, it claims that CFA/I pili could be synthesised without CfaE (Jansson et al., 2006). Our studies indicate that, contrary to the existing model, CfaB does not bind asialo- GM1 independently of CfaE. Neither isolated CfaB subunits nor CfaB assembled into pili bind to asialo-GM1. Instead, we demonstrated that binding activity for asialo-GM1 resides in CfaE and is essential for pilus binding to intestinal epithelial cells. We concluded that the binding activities of CFA/I pili for asialo-GM1, erythrocytes and intestinal cells are inseparable, depend on the same amino acid residues in CfaE and therefore represent the same or very similar binding mechanisms.

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Thesis (PhD Doctorate)
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Doctor of Philosophy (PhD)
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School of Medical Science
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Subject
Enterotoxigenic Escherichia coli (ETEC)
Traveller’s diarrhea
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