Emergence of Plasmid-Mediated Resistance Genes tet(X) and mcr-1 in Escherichia coli Clinical Isolates from Pakistan

The emergence of tet(X) represents a significant threat to human health. In this study, we aimed to investigate the genomic characterizations of tet(X)-positive clinical Escherichia coli isolates and provide genomic insight into the dissemination of antibiotic-resistant bacteria in clinical settings. Four tet(X)-positive E. coli isolates, PK5074, PK5086, PK5095, and PK5097, from 100 human clinical isolates were identified by PCR and were resistant to tigecycline. tet(X) genes were in IncFII plasmids in 4 E. coli isolates. Worryingly, PK5074 also carried an mcr-1-bearing IncHI2 plasmid. Notably, a relatively high cotransfer frequency of tet(X) and mcr-1 in PK5074 was found. PK5086, PK5095, and PK5097 were categorized into sequence type 410 (ST410) and indicated clonal dissemination of tet(X)-positive strains in hospitals, but tet(X)-bearing plasmids in PK5086, PK5095, and PK5097 were nontransferable. We present the first report of clinical E. coli isolates harboring tet(X) in South Asia. Our results support the implication of humans as a potential reservoir for tet(X)-harboring E. coli. We provide insight into the dissemination of tet(X) and mcr-1 in a clinical setting and highlight the current transmission of both critical resistance genes globally. IMPORTANCE Global transmission of plasmid-mediated tigecycline resistance gene tet(X)-bearing Escherichia coli strains incurs a public health concern. However, the research focusing on the prevalence of tet(X)-positive isolates in clinical specimens is still rare, and to our knowledge, there is no such report from South Asia. Here, we characterized four E. coli clinical isolates harboring tet(X) of human origin in Pakistan and demonstrated clonal dissemination of tet(X)-positive isolates in hospitals. We report the emergence of an mcr-1-bearing IncHI2 plasmid together with a tet(X)-positive IncFII plasmid in one clinical isolate. Cotransfer of tet(X)- and mcr-1-carrying plasmids is worrying and warrants further investigations.