Biochemical Studies & Biomolecular Homology Modeling (Structural Bioinformatics) of Biologically Important Toxin Proteases from Vibrio Cholerae
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Date
2009
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Center of Biotechnology & Microbiology, University of Peshawar
Abstract
At the molecular level, the pathogenesis of cholera is a multifactorial process. Several genes encoding virulence factors aid the pathogen in its colonization, coordinated expression of virulence factors, and toxin action such as cholera toxin (CT) and the toxin-regulated pilus (TCP). Cholera Toxin is primarily responsible for the profuse secretory diarrhea while the toxin-coregulated pilus is an essential colonization factor and receptor for the phage encoding CT. In addition to potent CT, there are other putative toxic factors such as accessory cholera enterotoxin (Ace), zonula occludens toxin (Zot), hemolysin/cytolysin and hemagglutinin/protease (Vibrioysin). Neuraminidase, a sialidase, is also considered a virulence factor. It is a key glycoside hydrolase that catalyzes the conversion of higher-order gangliosides to monosialoganglioside, which is the cholera toxin receptor. It has been hypothesized that neuraminidase may locally produce high concentration of the GM1 receptor for CT, thereby enhancing the binding and internalization of CT and resulting in greater efflux of water and electrolytes.
The present study comprises the analysis of toxin proteases of V. cholerae in order to have a better understanding of pathogenesis using molecular biology and bioinformatics tools as the signaling cascades involved in the induction and regulation of mucosal inflammatory responses to infection by V. cholerae are still largely unknown. The proposed work is carried out in two phases. The first phase deals with the mRNA expression of proinflammatory, anti-inflammatory and various other cytokines in intestinal tissue and bone marrow cells upon infection with purified Cholera Toxin (CT) alone and in combination with purified neuraminidase from Vibrio cholerae in order to elucidate the mechanisms of the V. cholerae induced proinflammatory response as well as