The human pathogen Vibrio cholera (V. cholerae) causes cholera, an infectious and often fatal disease of the small intestine. The disease is prevalent in infected water supplies — particularly in developing countries — and causes severe vomiting and diarrhea. Many who contract cholera have mild symptoms that are easily treated with oral rehydration solutions, but severe cases require rapid treatment with intravenous fluids and antibiotics. Cholera remains a global threat to public health, with nearly 4 million cases diagnosed and over 100,000 deaths per year.
With the help of a five-year, $1.8 million grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, researchers at Wayne State University are using a new zebrafish animal model to better understand how V. cholerae acts as a human pathogen, enabling future research to identify new therapeutic treatments as well as targets for environmental remediation. The grant is entitled “Mechanisms for Vibrio cholerae colonization and pathogenesis in zebrafish.”
Jeffrey Withey, PhD, associate professor of microbiology, immunology and biochemistry in Wayne State’s School of Medicine, will study the entire infectious cycle of the bacteria, from colonization of the intestine to production of diarrhea to transmission of the bacteria to new hosts. In addition, the team will study how V. cholera competes with the fish intestinal microbiota.
“Our goal is to better understand the infectious cycle and the genes involved in causing the disease so that we can devise better treatments for cholera patients in the future,” said Withey. “Animal models have been useful in characterizing major V. cholerae virulence factors, but animals used to date are not natural hosts of the infection and require absent or damaged microbiota to enable colonization. Vertebrate fish are natural hosts of V. cholerae, and we have established zebrafish as a model that recapitulates the entire infectious process in the presence of intact intestinal microbiota.”
The fish model presents new opportunities to study the disease in ways that have not been possible with mammalian models. Withey and his research team will examine the infectious processes to help advance knowledge of the environmental lifestyle of V. cholerae in a natural reservoir system and the requirements for V. cholerae to become a pathogen. The team will also look for new targets for therapies, environmental remediation and disease prevention — all to help combat V. cholerae disease and transmission in humans.
Source: Wayne State University