Emergence of tmexCD1-toprJ1 in the clinical high-risk clone sequence type 147 among carbapenem–resistant Klebsiella pneumoniae isolates in China: A multicentre retrospective study

The plasmid-mediated tigecycline resistance gene tmexCD1-toprJ1 and its variants have emerged as a public health threat, with increasing identification in various sources of Enterobacterales worldwide. However, comprehensive epidemiological features of tmexCD1-toprJ1 in clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) remain limited. Herein, we conducted a retrospective nationwide surveillance to assess the prevalence and molecular epidemiology of clinical tmexCD1-toprJ1-positive isolates from 4314 non-duplicated CRKP strains collected from 151 medical institutions across 31 provinces, municipalities, and autonomous regions in China. tmexCD1-toprJ1 was detected in 18 (0.42%) CRKP strains spanning 12 provinces, all exhibiting multidrug resistance phenotypes. ST147 was the dominant sequence type and predominantly co-harbored blaKPC-2. Phylogenetic analysis unveils the intrahospital, interhospital, and interprovincial spread of tmexCD1-toprJ1 carrying ST147 CRKP, which display a closer genomic proximity to those from other global regions, suggesting the international transmission risk of tmexCD1-toprJ1. Variable tigecycline resistance levels among isogenic ST147 strains were associated with differential tmexCD1-toprJ1 expression. Further, three types of plasmid replicons were found in the carriage of tmexCD1-toprJ1, among which IncFIB(K) and IncFIB(K)/IncHI1B were the primary vectors of tmexCD1-toprJ1, and a multireplicon megaplasmid was identified. The emergence of regionally disseminated tmexCD1-toprJ1-bearing ST147 CRKP clone highlights the potential global spread risk of tmexCD1-toprJ1, underscoring the urgent need for further surveillance and control measures to mitigate the ongoing spread of this resistant pathogen.