Conjugative plasmids facilitate the transmission of tmexCD2-toprJ2 among carbapenem-resistant Klebsiella pneumoniae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to global public health. The emergence of tmexCD-toprJ greatly weakened the efficacy of tigecycline in the treatment of CRKP infections. In this study, we did a comprehensive investigation of the prevalence and genomic features of tmexCD-toprJ in clinical CRKP from 2018 to 2020 in Henan province, China. The results demonstrated tmexCD-toprJ was at a low prevalence in CRKP from patients (7/2031, 0.34 %). Among the seven tmexCD-toprJ positive CRKP, KP18-29 that carried tmexCD1-toprJ1, blaNDM-1 and mcr-8.2 was resistant to tigecycline, carbapenem and colistin simultaneously. While, tmexCD2-toprJ2 together with one or two carbapenemase genes were detected in the remaining strains. Four strains (KP18-231, KP18-2110-2, KP19-3023 and KP19-3088) isolated at different times but shared the same sequence type (ST) 2667 exhibited high genomic similarity, indicating the clonal dissemination of CRKP ST2667 co-producing KPC-2 and TMexCD-TOprJ. Notably, conjugative transmission of the IncFrepB(R1701) plasmid co-harboring tmexCD2-toprJ2 and blaKPC-2 among clinical CRKP isolates belonging to different STs (ST2667, ST978 and ST147) revealed further propagation of tmexCD-toprJ among K. pneumoniae. Such IncFrepB(R1701) plasmids pose a substantial threat to public health due to their mobile resistance to both tigecycline and carbapenem. Online data mining showed isolates carried both carbapenemase genes and tmexCD-toprJ were dominantly isolated from humans, and isolates of animal origins usually carried mcr genes and tmexCD-toprJ, suggesting that these critical resistance genes co-existed in diverse niches. Global surveillance of K. pneumoniae co-harboring tmexCD-toprJ and mcr/carbapenemase genes in various settings with a One Health strategy was warranted.