Toxins force construction of roads to nowhere: Discovery is first report of effect on the abundant actin protein

Toxins released by a type of bacteria that cause diarrheal disease hijack cell processes and force important proteins to assemble into “roads to nowhere,” redirecting the proteins away from other jobs that are key to proper cell function, a new study has found.

The affected proteins are known as actins, which are highly abundant and have multiple roles that include helping every cell unite its contents, maintain its shape, divide and migrate. Actins assemble into thread-like filaments to do certain work inside cells.

Researchers found that two toxins produced by the Vibrio genus of bacteria cause actins to start joining together into these filaments — which could be thought of as cellular highways on which cargo is delivered — at the wrong location inside cells, and headed in the wrong direction.

“Growing in the wrong direction is a totally new function that was not previously known and was not thought to be possible for actin filaments inside the cell,” said senior author Dmitri Kudryashov, associate professor of chemistry and biochemistry at The Ohio State University. “A large fraction of actin in the cell is consumed in formation of the ‘highways’ where they are not needed, so the cell resources are wasted and cannot be used to satisfy the cell’s basic needs.”

The research is published today (Nov. 18, 2022) in the journal Science Advances.

These disruptive toxins are called VopF and VopL, and are produced by two strains of Vibrio bacteria living in seawater: V. cholerae and V. parahaemolyticus, both of which can contaminate oysters and other shellfish that, when eaten raw, make people sick.

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