Genetic “bonus material” makes the gut bacterium Segatella copri oxygen-tolerant

© HZI / Mathias Müsken

However, even though the oxygen tolerance of Segatella copri was low, the scientists concluded that the bacteria must possess a strategy that helped them survive under the influence of oxygen. But what was it? To find out, they exposed Segatella copri to oxygen for a few minutes in subsequent experiments and then performed a so-called transcriptome analysis. This allows researchers to determine which genes are active at a given time. “In Segatella copri, we identified the known transcription regulator PerR, which controls a genetic network that is crucial for the bacterial oxygen response,” says Youssef El Mouali. “In a mouse model, we were also able to show that Segatella copri cannot colonize the gut without the presence of PerR. PerR is therefore crucial for this bacterium to successfully colonize the gut.”

To investigate whether Segatella copri might possess additional regulatory mechanisms to survive oxygen stress, the researchers combed through databases and examined several hundred genomes of different strains of Segatella copri. A genome is the complete set of genes of an organism. They specifically searched for genetic traces of the transcription regulator OxyR, which regulates the oxygen response in bacteria of the genus Bacteroides, among others. And indeed, they found some strains of Segatella copri that possessed OxyR. The strains the researchers had used for the experiment to investigate oxygen tolerance, however, did not possess OxyR. The researchers therefore repeated the experiment specifically with strains containing OxyR to test whether these could handle oxygen better. And indeed: The strains of Segatella copri with OxyR exhibited a hundred to a thousand times higher oxygen tolerance than strains without OxyR. But how is it that some strains possess OxyR and others do not? “Our investigations suggest that a so-called horizontal gene transfer likely took place several thousand years ago. In this process, bacteria—sometimes even of different species—exchange genes with one another,” explains Till Strowig. 

In further investigations supported by the team of Nicola Segata at University of Trento, the researchers explored where in the world strains of the gut bacterium Segatella copri with and without OxyR occur in the human microbiome. To do this, they conducted extensive genomic data analyses and found that strains of Segatella copri with OxyR occur primarily in industrialized countries, whereas they are significantly rarer in African and most Asian countries. But why is that? “We suspect that bacterial strains of Segatella copri with OxyR have a selective advantage in highly industrialized countries,” says Till Strowig. “On the one hand, because disturbances in the gut’s balance occur more frequently here—for example, due to antibiotic use—which can temporarily lead to increased oxygen availability in the gut. On the other hand, human-to-human transmission could also be challenging due to higher hygiene standards. Better oxygen tolerance, allowing the bacterium to survive longer periods in the open air until transmission to the next host, could be quite helpful for the exclusively gut-dwelling bacterium Segatella copri.”

With their study, the researchers were able to impressively demonstrate that gut bacteria of the same species can exhibit such decisive genetic differences at the strain level that they lead to entirely different characteristics and adaptive abilities under changing environmental conditions. In future research projects, Till Strowig’s team plans to investigate how intestinal colonization by Segatella copri—depending on the strain, with or without the genetic bonus material from OxyR—affects human health.

Text: Nicole Silbermann