Emergence of a Novel Plasmid-Mediated Tigecycline Resistance Gene Cluster, , in Klebsiella quasipneumoniae and Enterobacter .

The occurrence of transferable tigecycline resistance determinants, , , , and multiple (A) and (X) variants, presents an unprecedented challenge to clinical therapeutic options. -like gene clusters can mediate multidrug resistance and have been detected in a variety of bacteria. Here, we characterized the fourth -like gene cluster, , identified on untypeable plasmids of Klebsiella quasipneumoniae and Enterobacter roggenkampii isolated from chicken meat and environmental samples from farm markets, respectively. TMexCD4-TOprJ4 was closely related (92 to 99% amino acid identity) to TMexCD1-TOprJ1, TMexCD2-TOprJ2, and TMexCD3-TOprJ1. Phylogenetic analysis revealed that was not in the same branch as the other three variants. Expression of increased tigecycline efflux in Escherichia coli and resulted in a 4- to 8-fold increase in MICs of tigecycline in E. coli and Klebsiella pneumoniae. Moreover, can act synergistically with its upstream gene (A) to reduce the susceptibility of E. coli and K. pneumoniae strains to tigecycline. The containing plasmid is a novel plasmid type and can be transferred to E. coli and K. pneumoniae only via electrotransformation. The increasing emergence of plasmid-mediated tigecycline resistance gene clusters suggests that the spread of -like gene clusters requires widespread attention. The plasmid-mediated tigecycline resistance gene cluster and other variants have been detected in a variety of strains from multiple sources, including human-derived strains. In addition to tigecycline, these -like gene clusters reduce susceptibility of the host strain to many other antimicrobials. Here, we identified in and , suggesting that this gene cluster is already present in the human-associated environment and the risk of transmission to humans is increased. Monitoring tigecycline-resistant Gram-negative bacteria is essential for understanding and addressing the spread of this gene cluster in agriculture and health care.