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Sticky situation? Insights into what holds antibiotic-resistant biofilms together

Biofilms, ubiquitous bacterial communities embedded in a slimy matrix, are the oldest form of multicellularity on Earth; they are extremely resistant to antibiotics and stick tenaciously to most surfaces, including living tissue.

While it is commonly assumed that biofilm cells are glued together by that matrix—a complex shared home comprised of extracellular polymeric substances—the biochemical dynamics that underpin these interactions are not well understood.

In a new study, a team of Yale researchers sought to understand how these bacteria come together, recognize each other, and then break out of their sticky matrix, reproduce, and spread. Better understanding of the molecular and biophysical interactions within biofilm communities, researchers say, could lead to new strategies to combat infection related to biofilms, which are hard to treat using traditional antibiotics.

Using a combination of genetics, microscopy, simulations, and biochemical analyses, the research team, led by Jing Yan, assistant professor of molecular, cellular and developmental biology in Yale's Faculty of Arts and Sciences, sought to uncover how Vibrio cholerae (the bacterium responsible for cholera) sticks together to form biofilms—and also escape and create new communities.

The study is in the journal Nature Communications.

The matrix covering the bacterial colony, researchers say, is composed mainly of exopolysaccharides (EPS), or long sugar chains. But the team found that the purified EPS, contrary to long-held belief, isn't really sticky to the cells at all. Rather, they found, it repels those cells that do not produce EPS.

They found that bacteria that are diligently making EPS naturally attract each other—and exclude the lazy ones that don't pay the cost of making EPS but are still trying to get into the cell matrix.

"It is like a membership card," said Yan, who is also a member of the Quantitative Biology Institute at Yale. "If you pay the price to make EPS, you are welcomed into the club."

As the biofilm ages, however, bacteria remodel their surfaces to flip the interactions between EPS-producing cells and the matrix from attractive to repulsive, the research team found. This, they said, allows the bacteria to escape and then form new colonies.

"This smart strategy helps the bacteria disperse as groups, ready to colonize new environments," said Alexis Moreau, a postdoctoral researcher in Yan's lab and lead author of the study.