Virulence and Genomic Feature of a Virulent Klebsiella pneumoniae Sequence Type 14 Strain of Serotype K2 Harboring blaNDM–5 in China

Abstract

The objective of this study was to reveal the molecular mechanism involved in carbapenem resistance and virulence of a K2 Klebsiella pneumoniae clinical isolate 24835. The virulence of the strain was determined by in vitro and in vivo methods. The de novo whole-genome sequencing technology and molecular biology methods were used to analyze the genomic features associated with the carbapenem resistance and virulence of K. pneumoniae 24835. Strain 24835 was highly resistant to carbapenems and belonged to ST14, exhibited hypermucoviscous and unique K2-aerobactin-kfu-rmpA positive phenotype. As the only carbapenemase gene in strain 24835, blaNDM–5 was located on a 46-kb IncX3 self-transmissible plasmid, which is a very close relation of pNDM-MGR194 from India. Genetic context of blaNDM–5 in strain 24835 was closely related to those on IncX3 plasmids in various Enterobacteriaceae species in China. The combination of multiple virulence genes may work together to confer the relative higher virulence in K. pneumoniae 24835. Significantly increased resistance to serum killing and mice mortality were found in the virulent New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae strain compared to the other NDM-producing K. pneumoniae strain. Our study provides basic information of phenotypic and genomic features of K. pneumoniae 24835, a strain displaying carbapenem resistance and relatively high level of virulence. These findings are concerning for the potential of NDM-like genes to disseminate among virulent K. pneumoniae isolates.

Pathogenomics and Evolutionary Epidemiology of Multi-Drug Resistant Clinical Klebsiella pneumoniae Isolated from Pretoria, South Africa

“…Fortunately, no hypervirulence genes were found albeit capsule type K2, identified in some strains ( Figs. 9-12), are associated with increased virulence and resistance [67][68][69] . It is interesting to note that the K2 serotype was also identified in a ST14 strain (K118) in this study as was reported in China recently 69 .…”

Hypervirulent Klebsiella pneumoniae: a new public health threat

“…Conversely, Gu and colleagues [13] have reported acquisition of a hvKp virulence plasmid by a carbapenem-resistant cKp strain, which caused an outbreak of 5 cases in a Chinese hospital ICU, and uniformly fatal outcomes in the patients affected. A strain of hvKp possessing bla NDM-5 has also been described [14]. In light of these data, it is probable that further convergence of multidrug resistance genes with hypervirulent K. pneumoniae will occur.…”

Klebsiella pneumoniae: an increasing threat to public health

“…Once the bla KPC-2 gene is introduces into a certain location, especially in a hospital setup, under antibiotic selection pressure, further dissemination of this gene may occur which may lead to MDR and XDR strains. Hypermucoviscous K. pneumoniae (HMKP) strain types which are sporadically distributed in Asia and the Middle East are the NDM-producing isolates [12,13]. Liu et al [14], had reported the first outbreak of CR-HMKP strains which harbored bla NDM-1 gene, shared the same pulsotypes (PT) and belong to the same Sequence types (ST).…”