Researchers use AI to detect new family of genes in gut bacteria

UT Southwestern researchers use AI to detect 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 detection genes in gut bacteria that are linked by structure and likely 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 bacterial intestinal infections.

“We identified similarities in these proteins in the reverse order of how it’s usually done. Instead of using sequence, Lisa looked for similarities in their structure,” said Kim Orth, Ph.D., professor of Molecular Biology and Biochemistry, who co-authors led the study with Lisa Kinch, Ph.D., a bioinformatics specialist in the Department of Molecular Biology.

The lab of Dr. Orth has long focused on studying how the sea and estuary bacteria cause infections. In 2016, Dr. Orth and her colleagues biophysics to characterize the structure of two proteins, called VtrA and VtrC complex, that work together in a 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 crustaceans — detects bile from the bacterial cell surface and sends a signal to launch a chemical cascade that kills this microbe. to invade the intestinal cells of its human host.

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

“We had never seen anything like VtrC,” said Dr. chin. “But, we thought, other proteins like this must exist.”

Without any known genes with sequence identities similar to VtrC, the researchers turned to software released just two years ago called AlphaFold. This one artificial intelligence program can accurately predict the structure of some proteins based on the genetic sequence that encodes them — information previously gathered only through painstaking work in the lab.

AlphaFold showed that a egg white named ToxS in V. cholerae is very similar in structure to VtrC, although the two proteins did not share recognizable parts of their genetic sequences. When the researchers looked for proteins with similar structural features in other organisms, they found homologues for VtrC in several other gut bacteria responsible for human disease, including Yersinia pestis (which is the bubonic plague) and Burkholderia pseudomallei (which causes a tropical infection called melioidosis). Each of these VtrC homologs appears to interact with proteins similar in structure to VtrA, suggesting that their role could be similar to that in V. parahaemolyticus.

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

Study finds detection mechanism in food poisoning

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

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