Emergence of IS26-mediated pLVPK-like virulence and NDM-1 conjugative fusion plasmid in hypervirulent carbapenem-resistant Klebsiella pneumoniae.

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has been widely reported and poses a global threat. However, the comprehensive genetic structure of ST11-KL64 hv-CRKP and the possible evolutionary mechanisms from a genetic structure perspective of this high-risk clone remain unclear. Here, a blaKPC-2-blaNDM-1-positive ST11-KL64 hv-CRKP isolate was obtained from a human bloodstream infection (BSI). Whole-genome sequencing and bioinformatics analyses revealed that it contained a fusion plasmid, pKPTCM2-1. pKPTCM2-1 is a conjugative plasmid composed of an oriT-positive pLVPK-like virulence plasmid and a type IV secretion system-produced blaNDM-1-bearing IncX3 plasmid mediated by IS26-based co-integration. This progress generated 8-bp target site duplications (TGAAAACC) on both sides. The fusion plasmid possessed self-transferability and could be transferred to blaKPC-2-harboring ST11-KL64 CRKP to form the ST11-KL64 hv-CRKP clone. The pLVPK-like-positive ST11-KL64 strain exhibited virulence levels similar to those of the typical hypervirulent K. pneumoniae NTUH-2044. The mutation, Tet(A) (A276S), which was believed to lead to tigecycline resistance was observed. Overall, this high-risk clone has emerged as a tremendous threat in fatal BSIs and thus, targeted surveillance is an urgent need to contain the hv-CRKP clones.

Tian C ，Shi Y ，Ren L ，Huang D ，Wang S ，Zhao Y ，Fu L ，Bai Y ，Xia D ，Fan X ... -  《-》

Characterization difference of typical KL1, KL2 and ST11-KL64 hypervirulent and carbapenem-resistant Klebsiella pneumoniae.

Almost all the formation of hypervirulent and carbapenem-resistant Klebsiella pneumoniae follow two major patterns: KL1/KL2 hvKP strains acquire carbapenem-resistance plasmids (CR-hvKP), and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids (hv-CRKP). These two patterns may pose different phenotypes. In this study, three typical resistance and hypervirulent K. pneumoniae (KL1, KL2, and ST11-KL64), isolating from poor prognosis patients, were selected. Compared with ST11-KL64 hv-CRKP, KL1/KL2 hypervirulent lineages harbor significantly fewer resistance determinants and exhibited lower-level resistance to antibiotics. Notably, though the blaKPC gene could be detected in all these isolates, KL1/KL2 hvKP strain did not exhibit corresponding high-level carbapenem resistance. Unlike the resistance features, we did not observe significant virulence differences between the three strains. The ST11-KL64 hv-CRKP (1403) in this study, showed similar mucoviscosity, siderophores production, and biofilm production compared with KL1 and KL2 hvKP. Moreover, the hypervirulent of ST11-KL64 hvKP also verified with the human lung epithelial cells infection and G. mellonella infection models. Moreover, we found the pLVPK-like virulence plasmid and IncF blaKPC-2 plasmid was crucial for the formation of hypervirulent and carbapenem-resistant K. pneumoniae. The conservation of origin of transfer site (oriT) in these virulence and blaKPC-2 plasmids, indicated the virulence plasmids could transfer to CRKP with the help of blaKPC-2 plasmids. The co-existence of virulence plasmid and blaKPC-2 plasmid facilitate the formation of ST11-KL64 hv-CPKP, which then become nosocomial epidemic under the antibiotic stress. The ST11-KL64 hv-CPKP may poses a substantial threat to healthcare networks, urgent measures were needed to prevent further dissemination in nosocomial settings.

Zhou Y ，Wu C ，Wang B ，Xu Y ，Zhao H ，Guo Y ，Wu X ，Yu J ，Rao L ，Wang X ，Yu F ... -  《-》

Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring bla(KPC) and bla(NDM): implications for public health threat mitigation.

Wang Q ，Liu Y ，Chen R ，Zhang M ，Si Z ，Wang Y ，Jin Y ，Bai Y ，Song Z ，Lu X ，Hao M ，Hao Y ... -  《Annals of Clinical Microbiology and Antimicrobials》

Emergence of KPC-2 and NDM-5-coproducing hypervirulent carbapenem-resistant Klebsiella pneumoniae with high-risk sequence types ST11 and ST15.

Zhou Y ，Wu X ，Wu C ，Zhou P ，Yang Y ，Wang B ，Xu Y ，Zhao H ，Guo Y ，Yu J ，Yu F ... -  《mSphere》

Genetic characteristics of clinical carbapenem-resistant Klebsiella pneumoniae: epidemic ST11 KPC-2-producing strains and non-negligible NDM-5-producing strains with diverse STs.

Klebsiella pneumoniae is among the most important Gram-negative pathogens that can cause serious nosocomial infections. The emergence and prevalence of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) pose a significant challenge to public health. In this study, we characterized thirty carbapenem-resistant K. pneumoniae (CRKP) strains from a tertiary care hospital in Sichuan province, China, by whole-genome sequencing and genome analysis. These strains were all highly resistant to carbapenem but remained susceptible to tigecycline. Of the 30 tested CRKP strains, 23 were positive for blaKPC-2 and seven for blaNDM-5. These blaKPC-2-positive strains all belonged to ST11, while blaNDM-5-positive strains belonged to five distinct STs. Phylogenetic analysis revealed a predominant intra-hospital transmission of ST11-KL64 in KPC-2-producing CRKP, and that both clonal and horizontal transmission of blaNDM-5 have occurred among NDM-5-producing CRKP strains in this hospital. Hypervirulence genes were commonly detected in the CRKP. The prevalent pLVKP-like plasmid and ICEKp seem to have contributed largely to the transmission of virulence genes in them. blaNDM-5 was located on highly similar IncX3 plasmids in the collected strains, and its truncated vision was highlighted. blaKPC-2 was primarily carried by IncFII/IncR plasmids in our collection. At least two IncFII/IncR plasmid subtypes were identified, exhibiting high similarity to many previously reported blaKPC-2-bearing plasmids from different parts of China. The findings provide an expanded knowledge of the genetic characteristics of CRKP, the transmission pattern of carbapenem-resistance genes, and also the convergence of Hv-CRKP.

Yuan Y ，Lu Y ，Cao L ，Fu Y ，Li Y ，Zhang L ... -  《Scientific Reports》