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March 29, 2021

MSU researcher awarded NIH grant to study unknown genes found in cholera

Uncovering the genetics behind a six-decade long cholera pandemic is being funded with a $2.8 million National Institutes of Health grant awarded to a Michigan State University researcher leading the study.

Chris Waters, professor of microbiology and molecular genetics in MSU’s College of Osteopathic Medicine, said the research into 36 genes key to the persistence of cholera aims to increase understanding of how bacterial pandemics surface as well as boost development of new viral therapies to treat bacterial infections.

Cholera is a waterborne disease that lives in the environment and infects humans. This disease kills about 100,000 people each year and can be found throughout the world with recent outbreaks in Haiti, Yemen and Ethiopia. A novel cholera pandemic emerged in 1961 and continues today.

Chris Waters
Chris Waters

“We want to figure out why a new cholera pandemic reemerged and how it has persisted for the last 60 years,” said Waters, who also holds a joint appointment with MSU’s College of Natural Science.

Waters and longtime collaborator Matthew Neiditch, associate professor in the Department of Microbiology, Biochemistry and Molecular Genetics at Rutgers and co-investigator on the grant, sought to understand how 36 genes of unknown function acquired by the current cholerae pandemic strain contribute to its emergence and persistence. 

“These genes had never been seen in cholera before,” Waters said. “Up until recently, we didn’t know anything about them.”

 

One gene in particular discovered by Waters and his team was named DcdV. It's especially adept at defending cholera bacterium from cell-destroying therapeutic viruses called phages in that it hinders phages from replicating.

 

Understanding how DcdV prevents phages from multiplying may help researchers counter with the development of more effective phage therapy treatments for cholera as well as other antibiotic-resistant staph bacterial infections such as MRSA.

"We also found that DcdV is widespread in bacteria and even eukaryotic cells, like the ones found in our bodies,” Waters said. “There is a well-studied viral defense mechanism in humans called APOBEC proteins that defends against viruses like HIV. It belongs to the same enzyme family as DcdV, suggesting a common viral defense function in bacteria and humans.”  

Other researchers on the project include Janani Ravi, an assistant professor in the MSU Department of Pathobiology and Diagnostic Investigation; Kristin Parent, associate professor and John Dover, a lab manager, in the MSU Department of Biochemistry and Microbiology; MSU graduate student Brian Hsueh and former MSU graduate student Geoff Severin, both with Waters’ lab; and Professor Eva Top and graduate student Clint Elg from the University of Idaho through MSU's BEACON Center.




By: Emilie Lorditch

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