AUTHOR=Du Fang-ling , Huang Qi-sen , Wei Dan-dan , Mei Yan-fang , Long Dan , Liao Wen-jian , Wan La-gen , Liu Yang , Zhang Wei 

TITLE=Prevalence of Carbapenem-Resistant Klebsiella pneumoniae Co-Harboring blaKPC-Carrying Plasmid and pLVPK-Like Virulence Plasmid in Bloodstream Infections

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.556654

DOI=10.3389/fcimb.2020.556654

ISSN=2235-2988

ABSTRACT=<p>This study aimed to characterize carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (CR-KP) co-harboring <italic>bla</italic><sub>KPC-2</sub>-carrying plasmid and pLVPK-like virulence plasmid. Between December 2017 and April 2018, 24 CR-KP isolates were recovered from 24 patients with bacteremia. The mortality was 66.7%. Pulsed-field gel electrophoresis and multilocus sequence typing results indicated four clusters, of which cluster A (n = 21, 87.5%) belonged to ST11 and the three remaining isolates (ST412, ST65, ST23) had different pulsotypes (cluster B, C, D). The <italic>bla</italic><sub>KPC-2</sub>-carrying plasmids all belonged to IncFII<sub>K</sub> type, and the size ranged from 100 to 390 kb. Nineteen strains (79.2%) had a 219-kb virulence plasmid possessed high similarity to pLVPK from CG43 with serotype K2. Two strains had a 224-kb virulence plasmid resembled plasmid pK2044 from <italic>K. pneumoniae</italic> NTUH-K2044(ST23). Moreover, three strains carried three different hybrid resistance- and virulence-encoding plasmids. Conjugation assays showed that both <italic>bla</italic><sub>KPC-2</sub> and <italic>rmpA2</italic> genes could be successfully transferred to <italic>E. coli</italic> J53 in 62.5% of the strains at frequencies of 4.5 × 10<sup>−6</sup> to 2.4 × 10<sup>−4</sup>, of which three co-transferred <italic>bla</italic><sub>KPC-2</sub> along with <italic>rmpA2</italic> in large plasmids. Infection assays in the <italic>Galleria mellonella</italic> model demonstrated the virulence level of these isolates was found to be consistently higher than that of classic <italic>Klebsiella pneumoniae</italic>. In conclusion, CR-KP co-harboring <italic>bla</italic><sub>KPC-2</sub>-carrying plasmid and pLVPK-like virulence plasmid were characterized by multi-drug resistance, enhanced virulence, and transferability, and should, therefore, be regarded as a real superbug that could pose a serious threat to public health. Hence, heightened efforts are urgently needed to avoid its co-transmission of the virulent plasmid (gene) and resistant plasmid (gene) in clinical isolates.</p>