IME_Rho_tet, a novel family of putative integrative mobilizable elements spreading tetracycline resistance genes tet(W) and tet(32) among human and animal gut bacteria

Antimicrobial resistance remains a major global health concern in human and animal medicine. Tetracycline resistance genes of the ribosomal protection protein (RPP) family, especially <i>tet</i>(W), are among the most abundant resistance genes in livestock animals and human gut microbiota. However, genetic determinants responsible for the spread of <i>tet</i>(W) are not yet fully described. Here, all genomes of the phyla <i>Bacillota</i> and <i>Actinomycetota</i> available in RefSeq were screened for Tet(W)-related proteins as well as signature proteins of a new putative integrative mobilizable element (IME) recently described to carry the <i>tet</i>(W) gene. This element, hereafter named IME_Rho_tet, showed an extensive diversity, both for its relaxase and serine recombinase signature proteins and for the encoded tetracycline resistance protein. A total of 504 complete and 1,090 partial IME_Rho_tet elements were detected, of which 68% encoded Tet(W). The remaining IME_Rho_tet encoded other RPPs, including Tet(32), Tet(O) and the mosaic Tet(O/32/O), as well as a few novel RPP and variants. Overall, 71% of all <i>tet</i>(W) detected in bacteria isolated from human or animal gut were linked to IME_Rho_tet, as well as 87% of all <i>tet</i>(32). IME_Rho_tet elements showed an extensive bacterial host range, as complete elements were detected in more than 60 <i>Bacillota</i> genera, while partial elements were also detected in 20 <i>Actinomycetota</i> genera. Finally, eight of the ten mobile elements reported in the literature as carrying <i>tet</i>(W) or <i>tet</i>(32) included complete or partial IME_Rho_tet. These findings highlight the IME_Rho_tet family as a key genetic player in the dissemination of <i>tet</i>(W) and <i>tet</i>(32) among gut-associated bacteria of humans and food-producing animals.