Researchers use AI to discover new gene families in gut bacteria

UT Southwestern researchers use AI to discover a new family of genes in gut bacteria

Membrane signaling system of gut-infecting bacteria. Credit: UT Southwestern Medical Center

Using artificial intelligence, UT Southwestern researchers have discovered a new family of sensor genes in gut bacteria that are related by structure and possibly function, but not genetic sequence. The findings, published in PNASoffer a new way to identify the role of genes in unrelated species and could lead to new ways to fight intestinal bacterial infections.

“We identified similarities in these proteins in the opposite direction of the way it is normally done. Instead of using sequence, Lisa looked for matches in their structure,” said Kim Orth, Ph.D., professor of molecular biology and biochemistry, who co-led the study with Lisa Kinch, Ph.D., a bioinformatics specialist in the Department of Molecular Biology.

Dr. Orth’s lab has long focused on studying how the sea and the estuary bacteria cause infections. In 2016, Dr. Orth and her colleagues used biophysics to characterize the structure of two proteins called the VtrA and VtrC complex, which work together in bacterial species known as Vibrio parahaemolyticus. She and her team then discovered the VtrA/VtrC complex in V. parahaemolyticus—which is often the cause of food poisoning from contaminated shellfish—senses bile from the bacterial cell surface, sending a signal to start a chemical cascade that prompts this microbe to invade the intestinal tract. cells of its human host.

Although VtrA shares some structural features with a protein called ToxR found in a related bacterium called Vibrio cholerae, which causes cholera, it is unclear whether a homologue for VtrC also exists in this or any other bacterium.

“We’ve never seen anything like VtrC,” said Dr. Kinch. “But we thought there must be other proteins like it.”

Without any known genes with sequence identity similar to VtrC, the researchers turned to software released just two years ago called AlphaFold. This AI The program can accurately predict the structure of certain proteins based on the genetic sequence that codes for them – information that was previously gathered only through laborious work in the laboratory.

AlphaFold showed that a protein called ToxS in V. cholerae is very similar in structure to VtrC, although the two proteins do not share any recognizable parts of their genetic sequences. When researchers looked for proteins with similar structural features in other organisms, they found homologues for VtrC in several other species of intestinal bacteria responsible for human disease, including Yersinia pestis (which causes Plague) and Burkholderia pseudomallei (which causes a tropical infection called melioidosis). Each of these VtrC homologues appears to work in concert with proteins structurally similar to VtrA, suggesting that their roles may be the same as those in V. parahaemolyticus.

Dr. Orth said these structural similarities could eventually lead to pharmaceuticals that treat conditions caused by different infectious organisms that rely on similar pathogenic strategies.

Study finds sensitive mechanism in food poisoning

More info:
Lisa N. Kinch et al, Co-component signal transduction systems: Rapidly evolving virulence regulatory cassettes discovered in intestinal bacteria, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2203176119

Quote: Researchers use AI to discover new gene family in gut bacteria (2022, July 2) Retrieved July 2, 2022, from genes-gut-bacteria.html

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