Eating seafood raw can be poisoned: the "highway" of cells is diverted

A new study has found that a toxin released by a bacterium that causes diarrheal disease hijacks cellular processes, forcing important proteins to assemble into "nowhere to go," diverting proteins from other jobs
that are essential for the cell's normal function.
The affected protein, called actin, is abundant and has a variety of roles, including helping each cell bind its contents, maintain its shape, divide, and migrate
.
Actin assembles into thread-like filaments that do some work
inside the cell.
The researchers found that two toxins produced by Vibrio bacteria cause actin to begin connecting in the wrong place and direction within the cell into these filaments — filaments that can be thought of as cellular highways
that carry goods.

Senior author Dmitri Kudryashov, associate professor of chemistry and biochemistry at The Ohio State University, said: "Growing in the wrong direction is a completely new function that was previously known and did not think that actin filaments within cells were possible
.
Most of the actin in cells is consumed by the formation of 'highways' where they are not needed, so cellular resources are wasted and cannot be used to meet the basic needs
of cells.
”

The study was published today (November 18, 2022) in the journal Science Advances
.

Known as VopF and VopL, these damaging toxins are produced by two strains of Vibrio cholerae that live in seawater: Vibrio cholerae and Vibrio parahaemolyticus, both of which contaminate oysters and other shellfish and make people sick
when eaten raw.
In this study, the research team focused on describing unexpected cellular activity rather than any further implications, such as how hijacking is associated
with bacterial infection.

Elena Kudryashova, a research scientist in chemistry and biochemistry at The Ohio State University and first corresponding author, said: "We are studying this disturbance at the molecular level – we have not yet looked at how this cellular function affects humans
.
From a practical standpoint, this tells us more about these pathogens, and knowing your enemies helps you defeat them, but finding something we didn't know was possible — actin behaves in this way inside cells — raises new questions about whether this function might actually be needed, or might have been produced
in some other way.
”

Until now, it has been known that actin assembles each filament in a way, starting from the so-called tip and pointing to the barbed end
of the so-called structure.
Because of their limited number, actin can be broken down from the pointed end as needed and recycled to maintain directional activity toward the spiny end — these actin filaments then perform functions such as cell migration, contraction, or division
in response to cell instructions.

However, when VopF and VopL toxins enter cells, they attract actin molecules to begin forming new fibers and cause fibers to begin to aggregate at this point, which causes them to elongate in the direction of the tip — the opposite
of their usual elongation.

"The toxin starts making actin highways in the wrong place, forming something that is not beneficial to the cell, and the cell doesn't know what to do with it
," Kudryashov said.

This actin disturbance was observed with live-cell imaging containing individual toxin molecules
.
While they don't yet know all the consequences of this hijacking, the researchers say the results could include nutrients seeping through the damaged intestinal wall, which will provide food
for infectious bacteria waiting outside.

"Killing cells isn't always necessary — disrupting the cell's barrier function may also be beneficial
for pathogens," Kudryashova said.

That's why scientists want to know more about whether other molecules can force actin to coalesce into a "nowhere high-going" path, and whether strange fiber formation might even be a beneficial mechanism
in different environments.

"It's quite possible that our own cells are doing this in some cases, but we don't know because actin has so many functions that not all of them are well understood
," Kudryashov said.

Pointed-end processive elongation of actin filaments by Vibrio effectors VopF and VopL