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Study to establish zebrafish as functional animal model for V. cholerae

June 04, 2017

The zebrafish model, he said, is less expensive, simpler and more biologically relevant than existing V. cholerae models using mice or rabbits, neither of which is a natural host for the bacteria. Withey believes a zebrafish model should enable future researchers to identify the elusive signals for inducing V. cholerae virulence in humans.

"Identifying these signals should uncover new components of the virulence pathway, as well as new therapeutic targets," he said.

The second study, funded by a $361,000 grant, will focus on the bacteria itself, attempting to determine how V. cholerae senses and responds to signals to activate its expression of CT and other virulence factors that cause the symptoms of cholera. Withey also will try to track the complex regulatory cascade as the bacteria shuts down its virulence gene expression before escaping the host and returning to the environment.

In humans, bicarbonate is a major inducer of V. cholerae virulence and is found in high concentrations in the upper small intestine. Bile, also present in the small intestine, is another regulatory signal. Withey's studies are aimed at learning the mechanisms by which such signals cause V. cholerae to secrete CT and become toxic.

"Regulation of virulence gene expression is a common theme among bacterial pathogens, including well-known ones like salmonella or E. coli," he said. "These studies will significantly increase our understanding not only of V. cholerae pathogenesis, but of bacterial pathogens as a whole."

Source: Wayne State University - Office of the Vice President for Research