Scholars from the University of Texas Southwestern Medical Center recently discovered a new family of genes embedded in enteric bacteria through artificial intelligence. According to the experts, these specific genes are linked to structure and function but are not associated with the genetic sequence of the microbiome.
The study opens a novel approach to identifying a new set of genes in other species we know a few of and contributes to studies about possible ways to treat intestinal bacterial infections in the human gut.
Detecting New Gene Family in Gut Bacteria Through Structure
UT Southwestern's Department of Molecular Biology specialist and lead author of the study Kim Orth explained that their work identified similarities throughout the proteins present in the gut bacteria using a reverse approach to how the process is commonly carried out.
Instead of relying on the data from its sequence, the team considered analyzing the matches found in the bacteria's structure.
Orth's laboratory aims to determine the functions and methods marine and estuary bacteria utilize to infect other organisms. To proceed with the new study, Orth's team referred to their previous findings on two proteins known as VtrA and VtrC complexes.
Through biophysical principles, the researchers observed how the protein couple worked together in a bacterial species known as Vibrio parahaemolyticus. The VtrA/VtrC complex in the microbiome is considered the major factor in food poisoning from shellfish, reports PhysOrg.
In this 2016 study, Orth and colleagues found that the presence of the VtrA/VtrC complex in the Vibrio parahaemolyticus senses bile from the bacteria's cell surface and sends a signal afterward to emit a chemical cascade. This process triggers disruption in the intestinal cells of humans, which lead to many seafood poisoning cases.
Despite the VtrA proteins having similar features to the structure of a separate protein known as ToxR in cholera-inducing bacteria Vibrio cholerae, there is no sufficient information to link VtrC's sequence to the said microbe or any other species.
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AlphaFold AI Reveals Similarities of Genetic Protein Across Infectious Bacterias
Fellow UT Southwestern molecular biologist and co-author of the paper Lisa Kinch said that they had never seen any structure close to VtrC, but they are determined to find other existing proteins like it.
Due to the lack of data on the VtrC's sequence, the team used a new AI software called AlphaFold that can predict the structure of any proteins by analyzing information based on the genome sequence of the subject. This process was only possible in the past through a series of extensive laboratory work.
With the AlphaFold, the team saw great similarities between the structure of VtrC and a protein called ToxS in Vibrio cholerae. The two shared features but had no recognizable portions from each of their genetic sequences.
Pushing further, experts found that the VtrC homologs are also present in other enteric bacteria species known to inflict diseases on humans, such as the Burkholderia pseudomallei, the microbe behind the tropical infection melioidosis, and Yersinia pestis, the root of Bubonic plague.
In each of the bacteria, the VtrC sequence works well with their VtrA-like structures, suggesting that the roles found in the separate microbes are the same as those in Vibrio parahaemolyticus.
Orth said their work could add insights to the treatments and therapeutics for diseases caused by infections of organisms relying on similar pathogenic functions.
The study was published in the journal PNAS, titled "Co-component signal transduction systems: Fast-evolving virulence regulation cassettes discovered in enteric bacteria."
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