UW Professor Studies How Myxobacteria Form Social Groups

Microbes face many physical, chemical and biological challenges from their environments. In response, cells adapt. But whether they do so cooperatively is poorly understood.

A University of Wyoming professor led a research team on campus that studied how myxobacteria -- known as social predators that kill and consume other microbes -- that form social groups can cooperate with one another.

"We showed that myxobacteria that adapt to a stress -- in our case, detergent resistance -- can transfer that trait to naïve kin cells in a manner dependent on TraA/B, or outer membrane exchange. To our knowledge, this is the first time an adaption trait was shown to transfer from one cell to another, whether bacteria or a eukaryote, which are plants and animals," says Dan Wall, a professor in the UW Department of Molecular Biology. "We also surprisingly found these adapted or 'donor' cells benefited by sharing their adaption by forming a harmonious population where the former cells were not stressed by dying siblings in the presence of detergent."

Wall is senior author of a paper titled "Cell-cell transfer of adaptation traits benefits kin and actor in a cooperative microbe" that was published today (July 15) in the Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences that is an authoritative source of high-impact, original research that broadly spans the biological, physical and social sciences.

Kalpana Subedi, a former UW graduate student in Wall's lab, is the paper's lead author. She conducted most of the experiments and made significant contributions writing the paper, Wall says. Subedi received her Ph.D. in UW's Molecular and Cellular Life Sciences (MCLS) Program in 2022 and is now a scientist at MilliporeSigma in Laramie.

Deoxycholic acid, a component of bile detergent found in the gastrointestinal tract, and Tween-20, a common detergent used in molecular biology research, were used in the study to determine whether adapted traits are transferable to naïve kin.

"Cell-cell cooperation is mediated by a kin recognition system we discovered previously. This system uses the TraA and TraB cell-surface receptors to identify other kin bacterial cells that are highly related to them, for example, clonemates, which are genetically identical cells," Wall explains. "Once recognition occurs, cells exchange their cell material, meaning their proteins and lipids."

TraAB are cell-surface receptors that recognize other cells as self, analogous to how our immune system differentiates self from nonself, he says. Recognition occurs by TraA-TraA homotypic binding between two cells, where both cells must have matching pairs of TraA proteins. Specificity in recognition occurs because TraA receptors have highly variable sequences, meaning there are many different alleles of TraA in wild myxobacteria populations. Thus, binding and recognition only occur when both cells have the same TraA receptor/allele.

While Wall and his research team previously showed the outer membrane exchange was involved in kin discrimination where toxins were transferred and killed nonkin cells, Wall says the team hypothesized the outer membrane exchange system originally evolved to facilitate cooperation between self or clonal cells.

"But we needed an experimental approach to test this idea. This led us to test if cells that adapted to a particular environmental stress could transfer or share those beneficial adaption traits with their siblings by the TraAB system," he says. "Although we were uncertain about the potential outcome, we were pleased to find that, in some cases, adaption traits could be shared via the TraAB system as outlined in our PNAS paper."

The results were somewhat surprising, Wall says.

"Unexpectedly, we were surprised to find the adapted cells -- called actors in our title -- also benefited by sharing their adaption trait with their siblings," Wall says. "By doing so, both populations could thrive together in the presence of detergents. In contrast, if outer membrane exchange did not occur between the sibling cells, then both populations died."

Wall adds, "These findings give us a broader understanding of what microbes can do in biofilms; provide insights into how cells can cooperate; and evolutionary steps involved in multicellularity evolution."

Franco Basile, a professor in the UW Department of Chemistry; Brandon Saiz, a graduate teaching assistant in the Department of Chemistry and Ph.D. candidate in the MCLS Program; and Pravas Roy, a graduate research assistant in the Department of Molecular Biology and a Ph.D. candidate in the MCLS Program, are other authors of the paper.

The study was funded by grants from the National Institutes of Health's National Institute of General Medical Sciences. Supplemental funding was provided by UW INBRE (IDeA Networks of Biomedical Research Excellence) and Established Program to Stimulate Competitive Research (EPSCoR) grants.

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