Molecular epidemiology of carbapenem-resistant hypervirulent Klebsiella pneumoniae in China

The epidemiological features of the newly emerged carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) and its potential threat to human health are currently unknown. In this study, a total of 784 bla (KPC-2)-bearing CRKP strains collected from three hospitals located at different geographical locales in China during 2014-2017 were subjected to molecular typing, screening of virulence plasmid, string test and WGS (367/784 strains). The proportion of CRKP among all clinical K. pneumoniae strains increased sharply in China during 2014-2017. A large proportion (58%) of these CRKP strains were found to harbour a virulence-encoding plasmid, while only 13% of such strains exhibited a hypervirulent phenotype by string test and neutrophil assay. The lack of hypervirulent phenotype in virulent plasmid-bearing CRKP strains was found to be due to the mutation's presence on rmpA and rmpA2 genes, which rendered them non-functional, while some strains carrying wild type rmpA did not exhibit hypervirulent phenotype either suggesting that other factors might also contribute to the hypervirulence of CRKP. Phylogenetic and SNP analysis indicated that the transmission of these CRKP strains in China likely involved several major clones of ST11. Carriage of IncFII pSWU01-like, bla (KPC-2)-bearing plasmid was found to be the major mechanism of carbapenem resistance in these CRKP strains. In conclusion, our data indicated that the prevalence of CRKP strains carrying the virulence plasmid has rapidly increased in China, while genetic markers were not correlated well with the hypervirulent phenotypes, which call for a better definition and screening for these truly hypervirulent CR-HvKP strains in clinical settings.

Automated summary

The epidemiological features and potential threat to human health of the newly emerged carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) are currently unknown. This study analyzed 784 CRKP strains collected from three hospitals in China and found that the proportion of CRKP strains among clinical K. pneumoniae strains increased sharply. A significant number of these CRKP strains carried a virulence-encoding plasmid, but only a small percentage exhibited a hypervirulent phenotype. Genetic markers were not strongly correlated with hypervirulent phenotypes, indicating that additional factors may contribute to the hypervirulence of CRKP. The transmission of these CRKP strains in China likely involved multiple clones of ST11 and the major mechanism of carbapenem resistance was the carriage of IncFII pSWU01-like, bla (KPC-2)-bearing plasmids. These findings highlight the rapid increase in prevalence of CRKP strains carrying virulence plasmids in China and the need for better definition and screening of truly hypervirulent CR-HvKP strains in clinical settings.