Coexistence of plasmid-mediated tmexCD2-toprJ2 , bla IMP-4 , and bla NDM-1 in Klebsiella quasipneumoniae

Abstract

ABSTRACT Klebsiella quasipneumoniae is a potential pathogen that has not been studied comprehensively. The emergence of multidrug-resistant (MDR) K. quasipneumoniae , specifically strains resistant to tigecycline and carbapenem, presents a significant challenge to clinical treatment. This investigation aimed to characterize MDR K. quasipneumoniae strain FK8966, co-carrying tmexCD2-toprJ2 , bla IMP-4 , and bla NDM-1 by plasmids. It was observed that FK8966’s MDR was primarily because of the IncHI1B-like plasmid co-carrying tmexCD2-toprJ2 and bla IMP-4 , and an IncFIB(K)/IncFII(K) plasmid harboring bla NDM-1 . Furthermore, the phylogenetic analysis revealed that IncHI1B-like plasmids carrying tmexCD2-toprJ2 were disseminated among different bacteria, specifically in China. Additionally, according to the comparative genomic analysis, the MDR regions indicated that the tmexCD2-toprJ2 gene cluster was inserted into the umuC gene, while bla IMP-4 was present in transposon Tn As3 linked to the class 1 integron ( IntI1 ). It was also observed that an ΔTn 3000 insertion with bla NDM-1 made a novel bla NDM-1 harboring IncFIB(K)/IncFII(K) plasmid. The antimicrobial resistance prevalence and phylogenetic analyses of K. quasipneumoniae strains indicated that FK8966 is a distinct MDR branch of K. quasipneumoniae . Furthermore, CRISPR-Cas system analysis showed that many K. quasipneumoniae CRISPR-Cas systems lacked spacers matching the two aforementioned novel resistance plasmids, suggesting that these resistance plasmids have the potential to disseminate within K. quasipneumoniae . Therefore, the spread of MDR K. quasipneumoniae and plasmids warrants further attention. IMPORTANCE The emergence of multidrug-resistant K. quasipneumoniae poses a great threat to clinical care, and the situation is exacerbated by the dissemination of tigecycline- and carbapenem-resistant genes. Therefore, monitoring these pathogens and their resistance plasmids is urgent and crucial. This study identified tigecycline- and carbapenem-resistant K. quasipneumoniae strain, FK8966. Furthermore, it is the first study to report the coexistence of tmexCD2-toprJ2 , bla IMP-4 , and bla NDM-1 in K. quasipneumoniae . Moreover, the CRISPR-Cas system of many K. quasipneumoniae lacks spacers that match the plasmids carried by FK8966, which are crucial for mediating resistance against tigecycline and carbapenems, indicating their potential to disseminate within K. quasipneumoniae .