Functional and phylogenetic analysis of TetX variants to design a new classification system

Recently, many TetX variants such as Tet(X3 similar to 14) were reported to confer resistance to tigecycline which is a last-resort antibiotic used to treat infections caused by multidrug-resistant bacteria. In this study, we identified essential residues including 329, 339, 340, 350, and 351 in TetX variants that mediated the evolution of the tigecycline-inactive Tet(X2) enzyme to the active forms of Tet(X3) and Tet(X4). Based on their amino acid sequences and functional features, we classified TetX variants into TetX-A class, TetX-B class and TetX-C class. We further found that TetX-A class variants originated from Bacteroidetes, with some variants further evolving to TetX-C class and acquired by Enterobacteriaceae. On the other hand, our data showed that some variants genes belonging to TetX-A class evolved directly to TetX-B class, which was further transmitted to Acinetobacter spp. This new classification system may facilitate better clinical management of patients infected by TetX-producing strains.

Automated summary

In this study, essential residues in TetX variants that mediate the evolution of the tetecycline-inactive Tet(X2) enzyme to the active forms were identified. Based on their amino acid sequences and functional features, TetX variants were classified into three classes. Furthermore, the study showed the origin and transmission of different TetX variants, which may contribute to better clinical management of TetX-producing strains.