Winter 2019

Outsmarting Cholera

A cellular process identified by Tufts scientists could combat a half-century pandemic.

By Monica Jimenez

The tide is turning in a fifty-year war on a persistent strain of cholera, thanks to a team coled by Tufts scientists and their research on the molecule cGAMP.

In a study published in PNAS in June, Wai-Leung Ng, School of Medicine assistant professor of molecular biology and microbiology, and his colleagues at Tufts, Michigan State University, and Rutgers New Jersey Medical School have identified the function of cyclic GMP-AMP (cGAMP) in the El Tor biotype of the V. cholerae bacterium. The strain has largely replaced classical V. cholerae and is driving the current pandemic.

Illustration: Jenna Talbott / Shutterstock

According to the World Health Organization, cholera infects 1.3 to 4 million people each year, killing between 20,000 and 143,000 of them, mostly in African, Asian, and Latin American countries where access to clean water is limited. Although El Tor causes milder symptoms than the classical strain, it survives longer in the body and thus can potentially infect more people, Ng said. But exactly how El Tor displaced the classical strain is unknown.

Now Ng and his colleagues are a step closer to understanding. A molecule that’s also produced by human cells and associated with infections and cancer, cGAMP drew attention in 2012, when Harvard Medical School researchers found that it was also produced by El Tor—but not by classical V. cholerae. Ng and team have revealed cGAMP’s role as a signaling molecule for El Tor, controlling an enzyme that leads to changes in cell physiology that could be important in the pandemic’s evolution. “Our findings open up the black box for us to try to understand why this strain has become successful,” said Ng, who helmed the study with Michigan State University microbiology professor Chris Waters.

Formerly postdocs in the same lab at Princeton, Ng and Waters reconnected at a conference in Boston a few years ago and discovered both were studying the gene that codes for cGAMP in El Tor. “We were kind of surprised that we stumbled on the same thing coincidentally, but not that surprised, because we knew each other’s work,” Ng said. “We decided to collaborate, not compete, and harness the different expertise of our labs.”

The two have applied for an NIH grant to continue studying cGAMP’s function in El Tor—work that could pave the way for better vaccines and treatments. “The far-reaching goal,” Ng said, “is to use this knowledge to think about new, better ways to control cholera.”

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