Microbiologists and plant scientists find secret to tackling cholera

June 25, 2018, Michigan State University
Microbiologists and plant scientists find secret to tackling cholera. Credit: MSU

While cholera rages across many regions of the world, a team of microbiologists and plant scientists has pinpointed a genetic weakness in the pandemic's armor, which could lead to future treatments.

The current cholera began in Indonesia in 1961. Rather than fade away like its six previous worldwide outbreak predecessors, the responsible strain is thriving and actually picking up steam. A discovery, led by scientists from Michigan State University and Tufts University and featured in the current issue of PNAS, shows the key genetic change the seventh pandemic acquired to thrive for more than 50 years.

The interdisciplinary team of scientists reveal the first ever signaling network for a new bacterial signal, cyclic GMP-AMP (cGAMP), in the human cholera pathogen. The team also identified the first protein receptor of cGAMP as a phospholipase enzyme that remodels the V. cholerae membrane when cGAMP is produced.

"When this pandemic emerged, it virtually displaced all of the other V. cholerae isolates, or previous strains, on a worldwide scale," said Chris Waters, MSU microbiology professor, who co-led the study with Wai-Leung Ng, Tufts microbiologist. "No one really knows why this happened. Our discovery of cGAMP synthase and phospholipase, which are present only in the seventh pandemic, could be key drivers of the seventh cholera pandemic."

The evolution of this new signaling ability has contributed to this current strain—nicknamed "El Tor—in causing around 95,000 deaths annually. Just last year in Yemen, more than 1 million people contracted cholera and nearly 2,200 people died, making it one of the largest cholera outbreaks in world history.

Serendipity and interdisciplinary research contributed to this discovery. Even though they were postdoctoral fellows at Princeton University together, Waters and Ng didn't realize they were studying the same genetic pathway until they landed their positions at their respected universities.

Once they began to compare notes, they realized their research had real potential to understand this new cholera pandemic.

Graduate students Geoff Severin in the Waters lab and Miriam Ramliden in the Ng lab led the team to an island—the Vibrio seventh pandemic island—to find cholera's genetic advances that's allowed El Tor to find the traits none of its predecessors possessed. On this atoll of around 20 newly acquired genes was where they found the buried treasure of the phospholipase cGAMP receptor.

Waters knew that Christoph Benning, a renowned plant scientist and director of the MSU-DOE Plant Research Laboratory, was an expert in lipids and would possibly have some leads on the phospholipase—enzymes that degrade membrane building blocks—on which they were focusing.

"I immediately answered that yes we would like to help and that we could contribute to this research," Benning said. "If you break it down to the biochemistry, it doesn't matter if it's a human, bacterium or plant; we have many of the same genes and enzymes."

And indeed they did. Benning enlisted the help of Kenny (Kun) Wang, a former graduate student in his lab. Wang had become an expert on these types of plant proteins, which are tricky to produce as they can destroy cells in the process. He obtained and made the phospholipase work in a test tube so the team could study how it is controlled by cGAMP.

Now that the scientists have unearthed the treasure, they're looking for the keys to unlock one of El Tor's greatest strengths, and turn it against itself.

"We think this new system is one of the key elements that led to the emergence and persistence of the current pandemic," Ng said. "Our future research will try to understand the role that the cGAMP/phospholipase system played in this emergence."

Explore further: Risk of cholera epidemics estimated with new rule-book

More information: Geoffrey B. Severin et al. Direct activation of a phospholipase by cyclic GMP-AMP in El TorVibrio cholerae, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1801233115 , www.pnas.org/content/115/26/E6048

Related Stories

Risk of cholera epidemics estimated with new rule-book

November 9, 2017

Cholera has repeatedly traveled out of Asia to cause epidemics in Africa and Latin America, an international research team has found. Researchers at the Wellcome Trust Sanger Institute, Institut Pasteur in France, and collaborators ...

Fast-acting cholera vaccine could curb outbreaks

June 13, 2018

A tricked-out cholera vaccine starts protecting against the deadly disease within a day, experiments in rabbits suggest. The rapid protection offered by this designer vaccine may one day limit the spread of cholera outbreaks, ...

Cholera pandemic's source discovered

August 24, 2011

Researchers have used next generation sequencing to trace the source and explain the spread of the latest (seventh) cholera pandemic. They have also highlighted the impact of the acquisition of resistance to antibiotics on ...

Data gathering can't prevent a new influenza pandemic

March 22, 2018

Commenting on a new BBC Four programme, Contagion, presenting the results of an on-going citizen-scientist experiment investigating how a new influenza pandemic might spread across the UK, influenza expert Dr. Jeremy Rossman ...

Recommended for you

High vinculin levels help keep aging fruit fly hearts young

July 17, 2018

Our cells tend to lose their shape as we grow older, contributing to many of the effects we experience as aging. This poses particular problems for the heart, where aging can disrupt the protein network within muscle cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.