Identification of novel tetracycline resistance gene <i>tet</i> (X14) and its co-occurrence with <i>tet</i> (X2) in a tigecycline-resistant and colistin-resistant <i>Empedobacter stercoris</i>

Abstract

Tigecycline 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, <i>tet</i>(X14), was identified in a tigecycline-resistant and colistin-resistant <i>Empedobacter stercoris</i> strain 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) in <i>Escherichia coli</i> confers 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. <i>tet</i>(X14) and two copies of <i>tet</i>(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 that <i>tet</i>(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome of <i>Riemerella anatipestifer</i>, mainly encoded on antimicrobial resistance islands. <i>E. stercoris</i> and <i>R. anatipestifer</i> belong to the family <i>Flavobacteriaceae</i>, suggesting that the members of <i>Flavobacteriaceae</i> maybe the major reservoir of <i>tet</i>(X14). Our study reports a novel chromosome-encoded tigecycline resistance gene <i>tet</i>(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance for <i>tet</i>(X)-mediated tigecycline resistance.