A new study finds that toxins released by a bacterium that causes diarrheal disease hijack cell processes and force important proteins to assemble into “ways to nowhere,” redirecting proteins away from other functions that are central to proper cell function.
The affected proteins are known as actinides, which are extremely abundant and have multiple roles that include helping each cell to unite its contents, maintain its shape, divide, and migrate. Actinoids assemble into thread-like filaments to do some work inside cells.
Researchers found that two toxins produced by Vibrio The genus of bacteria causes the actinides to begin to clump together into these filaments—which can be thought of as cellular highways on which goods are transported—in the wrong location within cells, heading in the wrong direction.
“Growth in the wrong direction is a completely new function that was not previously known nor thought possible for actin filaments within a cell,” said senior author Dmitry Kudryashov, associate professor of chemistry and biochemistry at The Ohio State University. “A large portion of the cell’s actin is consumed forming ‘highways’ where it is not needed, so the cell’s resources are wasted and cannot be used to meet the basic needs of the cell.”
The research was published in the journal today (November 18, 2022). Science advances.
These destructive toxins are called VopF and VopL, and they are produced by two strains of Vibrio Bacteria that live in seawater: Vibrio cholera And the V. parahaemolyticusboth of which can contaminate shellfish and other shellfish that, when eaten raw, make people ill.
In this study, the research team focused on describing unexpected cellular activities rather than any other effects, such as the relationship of hijacking to bacterial infection.
“We’re looking at interference at the molecular level — we haven’t focused here on how this cell function affects humans,” said Elena Kudryashova, a research associate in chemistry and biochemistry at Ohio State.
“From a practical standpoint, this tells us more about pathogens, and knowing your enemy helps you fight your enemy,” she said. “But finding something we didn’t know was possible — for actin to behave this way inside a cell — raises new questions about whether this function might actually be necessary, or it could manifest itself in some other way.”
So far, actinides have been known to group all filaments in one way, originating from what is known as their pointed end and pointing towards the so-called barbed end of the structure. Being limited in number, actins are unrolled as needed from the pointed end and recycled to maintain directional activity toward the barbed end—thereby actin filaments perform functions, such as cell migration, contraction, or division, as dictated by what the cell orders.
However, when the VopF and VopL toxins enter the cell, they attract actin molecules to start new filaments and cause the filaments to begin to aggregate at this spot, causing them to elongate in the direction of the pointed tip—which is the opposite of their own. normal elongation direction.
“Toxins start making highways from actin filaments in the wrong place, building something that is useless to the cell, and the cell doesn’t know how to deal with it,” Kudryashov said.
This actinic overlap was observed using live cell imaging containing individual toxin molecules. Although they don’t yet know all the consequences of this hijacking activity, the researchers said the findings could include the leakage of nutrients through damaged gut walls – which would provide food for infectious bacteria waiting outside.
“Killing the cells is not always necessary — disrupting the barrier function of cells can also be beneficial for pathogens,” Kudryashova said.
Which is why scientists wanted to know more — whether other molecules could force actin to assemble “ways to nowhere,” and whether this strange filament formation might be a useful mechanism under a different set of circumstances.
“It’s very likely that our cells do this on some occasions, but we don’t know because actin has many functions and not all of them are well understood yet,” Kudryashov said.
The Ohio State team collaborated with co-authors Ankita, Heidi Ulrich, and Shashank Shekhar of Emory University.
This work was supported by grants from the National Institutes of Health.