Genetic characterization of clinical Escherichia coli strains that harbor the plasmid-borne tet(X4) gene in China

The tigecycline resistance gene tet(X4) has been widely reported in animals and animal products in recent years but only sporadically detected in human. To assess the potential public health threat of this resistance gene, we studied the prevalence and genetic features of tet(X4)-positive clinical E. coli strains. A total of 462 fecal samples were collected from patients in four hospitals located in four provinces in China in 2022. Nine tet(X4)-positive E. coli strains were isolated and subjected to characterization of their genetic and phenotypic features by performing antimicrobial susceptibility test and whole-genome sequencing. The majority of the test strains were found to exhibit resistance to multiple antimicrobial agents including tigecycline but remained susceptible to colistin and meropenem. A total of seven different sequence types (STs) and an unknown ST type were identified among the nine tet(X4)-positive strains. Notably, the tet(X4) gene in six out of these nine tet(X4)-positive E. coli strains were located in a IncFIA-HI1A-HI1B hybrid plasmid, which was a tet(X4)-bearing epidemic plasmid responsible for dissemination of the tet(X4) gene in China. Through expanding our understanding of epidemic tet(X4)-bearing plasmids and the tet(X4) genetic environment in clinical strains, our findings indicate that dissemination of such plasmids, which commonly encode resistance to multiple antimicrobial agents, is capable of causing further increase in the incidence of multidrug resistant infections in China.