Identification of novel tetracycline resistance genetet(X14) and its co-occurrence withtet(X2) in a tigecycline-resistant and colistin-resistantEmpedobacter stercoris

AbstractTigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene,tet(X14), was identified in a tigecycline-resistant and colistin-resistantEmpedobacter stercorisstrain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) inEscherichia coliconfers 16-fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s.tet(X14) and two copies oftet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting thattet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome ofRiemerella anatipestifer, mainly encoded on antimicrobial resistance islands.E. stercorisandR. anatipestiferbelong to the familyFlavobacteriaceae, suggesting that the members ofFlavobacteriaceaemaybe the major reservoir oftet(X14). Our study reports a novel chromosome-encoded tigecycline resistance genetet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance fortet(X)-mediated tigecycline resistance.