The leading cause of acute gastroenteritis linked to eating raw seafood disarms a key host defense system in a novel way: It paralyzes a cell’s skeleton, or cytoskeleton.

That finding, from UT Southwestern Medical Center, was reported in the journal PLoS Pathogens.

Without a working cytoskeleton, infected cells are unable to produce defensive molecules called reactive oxygen species (ROS) that normally attack bacterial DNA, said Dr. Marcela de Souza Santos, lead author of the study and a postdoctoral researcher in the laboratory of senior author Dr. Kim Orth. Dr. Orth is a Professor of Molecular Biology and Biochemistry at UT Southwestern as well as an Investigator in the prestigious Howard Hughes Medical Institute.

“Vibrio parahaemolyticus bacteria deploy a needlelike apparatus called a Type III Secretion System (T3SS) that injects toxic bacterial proteins, known as effectors, into cells that line the intestine, resulting in severe gastroenteritis,” Dr. de Souza Santos said.

Usually V. parahaemolyticus causes only a few days of gastrointestinal distress in the form of vomiting or diarrhea. On rare occasions, however, particularly in people with chronic health conditions like diabetes or liver disease that compromise the immune system, the bacteria can escape from the gut and enter the bloodstream, causing life–threatening systemic infection.

The Centers for Disease Control and Prevention (CDC) estimates Vibrio cause 80,000 illnesses and 100 deaths in the U.S. annually. Of those, an estimated 45,000 people are sickened by V. parahaemolyticus. Another Vibrio strain, V. vulnificus, can cause life–threatening infections in people with open wounds exposed to warm seawater. As with other Vibrio strains, people who are immunocompromised are at highest risk.

The CDC’s fact sheet says that 80 percent of U.S. vibriosis infections occur between May and October.

The state of Alaska reported its first V. parahaemolyticus outbreak in July 2004. Another strain of Vibrio sickened more than 80 people exposed to contaminated seawater during a heatwave in Northern Europe in 2014. The first Vibrio strains were identified in the 18th century.

Until recently, it was believed that Vibrio bacteria remained outside cells, doing their damage by shooting effectors into cells. However, in 2012, the Orth laboratory identified a way that V. parahaemolyticus tricks random cells lining the gut into engulfing the bacterium and bringing it inside the cell. The current study indicates how the T3SS protein VopL aids V. parahaemolyticus infection by helping the pathogen secure a niche within the cell for bacterial replication.

It’s a good strategy for a bacterium to infect random cells only, Dr. Orth said. If a pathogen were to infect most of the host’s cells quickly – as is thought to occur with the Ebola virus – the pathogen might kill its host so fast that it could undermine its own survival, she said.

In a study published last month in the journal Science Signaling, the Orth laboratory did something unprecedented: It followed V. parahaemolyticus infection over time – flash freezing samples every 15 minutes – to chart the pathogen’s effect on host signaling. That study identified 398 genes whose expressions were changed by Vibrio infection, said lead author and postdoctoral researcher Dr. Nicole De Nisco.

In the current study, the researchers found that one of V. parahaemolyticus’ many effectors – VopL – paralyzes the cytoskeleton through a novel mechanism. The cellular machinery, or complex, that makes the ROS sits on the cell surface, but the molecules that the cellular factory needs to assemble ROS are created inside the cell. A working, flexible cytoskeleton is necessary to move the molecules to the ROS factory, she explained.