Scientists created a model system to experimentally study tiny bacteria called TM7 and provide empirical data to confirm a hypothesis for how the bacteria adapted to live inside humans.

Among the diverse bacterial species living within our mouths is a group belonging to the Candidate Phyla Radiation (CPR). These bugs are especially mysterious because they are ultra-small, adopt a unique symbiotic lifestyle with their host bacteria, and most have yet to be cultured by scientists and studied in the lab. The only bacteria within the CPR to be examined in-depth are a group called TM7, which were cultivated for the first time by Forsyth Institute researcher Dr. Xuesong He in 2014.

In an important step toward better understanding these elusive bacteria, Dr. He and his collaborator, Dr. Jeffrey S. McLean at the University of Washington, have developed a new model system using the first isolated human oral TM7 strain, TM7x, and its host bacterium, Actinomyces odontolyticus. Researchers used the model system to experimentally study these tiny bacteria, testing a hypothesis for how TM7 adapted to live inside humans, and providing empirical data to confirm previous genomic studies. Their findings were published today in the journal Proceedings of the National Academy of Sciences (PNAS).

Scientists have found TM7 in many different environments, including soil, groundwater, and the bodies of other mammals. Studies have shown that while maintaining a remarkably similar genome overall, the TM7 found in human mouths are unique from those in other environments because they have acquired a gene cluster encoding the arginine deiminase system, or ADS.

«This was intriguing to us since there seem to be very few genomic changes that occurred in this group of tiny bacteria with already small genomes as they transitioned from the environment to mammals,» said Dr. McLean.

Researchers hypothesized that TM7 acquired ADS as an evolutionary advantage to help them adapt and survive in the human oral cavity. To test this hypothesis, Dr. Jing «Janet» Tian, first author of the study, used the model system to experimentally investigate the function and impact of ADS on TM7x and its host bacterium. She found that ADS helped TM7x break down arginine, a process that produces the compounds Adenosine triphosphate (ATP) and ammonia. The increased abundance of ATP and ammonia benefitted TM7x by increasing its infectivity, or ability to multiply. It also protected TM7x and its host bacterium from acid stress, a condition that microbes frequently encounter in the human oral cavity due to the acid created when bacteria feed on and metabolize dietary carbohydrates.

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