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

Abstract

This study aimed to characterize carbapenem-resistant Klebsiella pneumoniae (CR-KP) co-harboring blaKPC-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 blaKPC-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 blaKPC-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 blaKPC-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 blaKPC-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.

Genetic heterogeneity and predominance of blaCTX-M-15 in cefotaxime-resistant Enterobacteriaceae isolates colonizing hospitalized children in Tunisia

“…Similarly, carbapenemase-producing K. pneumoniae ST13 and ST37 clones have been reported as prevalent clones in various geographic regions, such as Portugal (Mendes et al 2022), Brazil (Rodrigues et al 2022) and Italy (Di Pilato et al 2021). The remaining STs were also rarely reported as carbapenemase-and/or ESBL-producing K. pneumoniae from many countries such as ST336 in Serbia (Novovi c et al 2017), ST219 in Russia (Fursova et al 2021) and ST412 in China (Du et al 2021). Since the reported carbapenemase-producing high-risk clonal lineages are also often ESBL producers, the occurrence of such ESBLproducing K. pneumoniae isolates colonizing those children is a cause of concern especially if these isolates acquire carbapenemase encoding genes.…”

“…2021) and ST412 in China (Du et al . 2021). Since the reported carbapenemase‐producing high‐risk clonal lineages are also often ESBL producers, the occurrence of such ESBL‐producing K. pneumoniae isolates colonizing those children is a cause of concern especially if these isolates acquire carbapenemase encoding genes.…”

Horizontal gene transfer via OMVs co-carrying virulence and antimicrobial-resistant genes is a novel way for the dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae

“…S1-PFGE was conducted to determine the plasmid location of transformants ( Du et al, 2020 ). Briefly, total DNA was embedded in agarose gel plugs.…”

Extensively Drug-Resistant Klebsiella pneumoniae Counteracts Fitness and Virulence Costs That Accompanied Ceftazidime-Avibactam Resistance Acquisition

“…Clinically, infections caused by hvKp are often invasive and include, for instance, pyogenic liver abscess, pneumonia, endophthalmitis, meningitis, necrotizing fasciitis, and bacteremia ( 22 ). Alarmingly, the convergence of both cKp and hvKp has already been frequently described ( 1 , 2 , 28 ), which blurs the boundaries between the pathotypes. This phenomenon is seemingly driven not only by the exchange of resistance ( 29 – 31 ) and virulence plasmids ( 28 , 32 ) but also by the chromosomal integration of DNA sequences with uncommonly high length ( 23 , 33 – 35 ) as well as rearranged “mosaic” plasmids that carry both resistance- and virulence-associated genes ( 1 , 36 – 38 ).…”

“…Alarmingly, the convergence of both cKp and hvKp has already been frequently described ( 1 , 2 , 28 ), which blurs the boundaries between the pathotypes. This phenomenon is seemingly driven not only by the exchange of resistance ( 29 – 31 ) and virulence plasmids ( 28 , 32 ) but also by the chromosomal integration of DNA sequences with uncommonly high length ( 23 , 33 – 35 ) as well as rearranged “mosaic” plasmids that carry both resistance- and virulence-associated genes ( 1 , 36 – 38 ). We have previously reported on such mosaic plasmids, which do not necessarily reduce bacterial fitness, in the above-mentioned ST307 K. pneumoniae clonal lineage ( 1 ).…”