Interactive networks of donors and recipients of the TetM gene and its evolutionary dynamics across the bacterial domain.

Identifying primary donors and recipients of the tetM gene is crucial for gaining a deeper understanding of the dynamics underlying the dissemination of resistance to tetracyclines in natural bacterial populations, including those of human and animal pathogens. This study modeled the major donor-recipient network of tetM, also providing important insights into the primary evolutionary mechanisms of this gene. The RDP4- and SplitsTree-embedded algorithms were used to detect genetic recombination events of tetM loci from different bacterial species and genera. FUBAR, MEME, and MEGA11 were employed to determine the evolutionary dynamics of this gene. A large tetM donor-recipient species network, exhibiting different bacterial genera, was determined based on the RDP4- and SplitsTree-generated inferences (P  ≤ 3.75E-02; bootstrap and fit values ≥ 90 and ≥ 94.9 respectively). 3 sites were identified as undergoing episodic diversifying selection, while 42 sites were under pervasive negative selection for this gene, with a discrete Gamma distribution value of 0.0500. Notably, Streptococcus agalactiae, Streptococcus equinus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, and Gardnerella vaginalis were suggested to be the predominant donors of tetM involved in inter-species and/or intergeneric recombination. Genetic recombination and pervasive negative selection were suggested to be the primary driving forces underlying the evolution of tetM.