Researchers have identified a new family of sensing genes in enteric bacteria using artificial intelligence that are related by structure and likely function but not genetic sequence. These findings offer a new way of identifying the role of genes in unrelated species and could lead to new ways to fight intestinal bacterial infections.
Similarities were identified in these proteins in reverse of how it’s usually done. Instead of using sequence, matches were looked for in their structure.
Studies on how marine and estuary bacteria cause infections have been focused upon for long now. In 2016, the structure of two proteins called VtrA and VtrC complex that function together in a bacterial species called Vibrio parahaemolyticus was characterized using biophysics. It was then discovered that this complex is often the cause of food poisoning from contaminated shellfish. It senses bile from the bacterial cell surface, sending a signal to launch a chemical cascade that prompts this microbe to invade the intestinal cells of its human host.
Although VtrA shares certain structural similarities with a protein called ToxR found in a related bacteria called Vibrio cholerae that causes cholera, it was unclear whether a homolog for VtrC also existed in this or any other bacteria.
Without any known genes with sequence identities similar to VtrC, the researchers turned to software released just two years ago called AlphaFold. This artificial intelligence program can accurately predict the structure of some proteins based on the genetic sequence that codes for them.
AlphaFold showed that a protein called ToxS in V. cholerae is very similar in structure to VtrC, even though the two proteins did not share any recognizable portions of their genetic sequences.
When the researchers searched for proteins with similar structural features in other organisms, they found homologs for VtrC in several other enteric bacteria species responsible for human diseases including Yersinia pestis (which causes the bubonic plague) and Burkholderia pseudomallei (which causes a melioidosis). Each of these homologs appear to work together with proteins structurally similar to VtrA, suggesting that their roles could be the same as those in V. parahaemolyticus.
These structural similarities may potentially result in medications to treat conditions caused by different infectious organisms that rely on similar pathogenic strategies.
Reference:
Lisa N. Kinch et al, Co-component signal transduction systems: Fast-evolving virulence regulation cassettes discovered in enteric bacteria, Proceedings of the National Academy of Sciences (2022).
Journal information:
Proceedings of the National Academy of Sciences
By Tushar Gupta
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