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Abstract
This study aimed to characterize carbapenem-resistant Klebsiella pneumoniae (CR-KP) co-harboring bla KPC-2-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 bla KPC-2-carrying plasmids all belonged to IncFIIK 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 K. pneumoniae NTUH-K2044(ST23). Moreover, three strains carried three different hybrid resistance- and virulence-encoding plasmids. Conjugation assays showed that both bla KPC-2 and rmpA2 genes could be successfully transferred to E. coli J53 in 62.5% of the strains at frequencies of 4.5 × 10−6 to 2.4 × 10−4, of which three co-transferred bla KPC-2 along with rmpA2 in large plasmids. Infection assays in the Galleria mellonella model demonstrated the virulence level of these isolates was found to be consistently higher than that of classic Klebsiella pneumoniae. In conclusion, CR-KP co-harboring bla KPC-2-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.
Highlights
Carbapenem-resistant Klebsiella pneumoniae (CR-KP) has emerged as one of the most challenging pathogens in the latest years (Holt et al, 2015)
The findings of this study provide insight into the current prevalence and features of carbapenem-resistant Klebsiella pneumoniae (CR-KP) co-harboring blaKPC-2-carrying plasmid and pLVPK-like virulence plasmid in a Chinese hospital
Nineteen strains (79.2%) had a 219-kb virulence plasmid possessed high similarity to previously reported pLVPK from Klebsiella pneumoniae CG43 with serotype K2
Summary
Carbapenem-resistant Klebsiella pneumoniae (CR-KP) has emerged as one of the most challenging pathogens in the latest years (Holt et al, 2015). The virulence plasmid carrying major virulence genes such as capsular polysaccharides regulator genes (rmpA and rmpA2) and those encoding siderophores (eg, iroBCDN, iucABCD, iutA) were recognized as essential contributors to the virulence of hypervirulent Klebsiella pneumoniae (hvKP), and might serve as potential biomarkers for hvKP. The loss of this pLVPKderived virulence plasmid significantly decreased virulence. CR-hvKP strains may emerge as a result of the acquisition of a carbapenemase-encoding plasmid by K1 or K2 hypervirulent Klebsiella pneumoniae (Zhang et al, 2016a). The high prevalence of carbapenem-resistant K pneumoniae (average 9.0% in 2017 and 15.4% in Jiangxi) and hypervirulent K pneumoniae (about 30–50%) (Zhang et al, 2016b; Liu and Guo, 2019) in Chinese hospitals may have contributed to the emergence of carbapenemresistant and hypervirulent microorganism
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