AUTHOR=Wu Chunyang , Zhou Ying , Ai Wenxiu , Guo Yinjuan , Wu Xiaocui , Wang Bingjie , Zhao Huilin , Rao Lulin , Wang Xinyi , Zhang Jiao , Yu Fangyou , Wang Liangxing 

TITLE=Co-occurrence of OXA-232, RmtF-encoding plasmids, and pLVPK-like virulence plasmid contributed to the generation of ST15-KL112 hypervirulent multidrug-resistant Klebsiella pneumoniae

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1133590

DOI=10.3389/fmicb.2023.1133590

ISSN=1664-302X

ABSTRACT=<p>The emergence of carbapenem-resistant <italic>Klebsiella pneumoniae</italic> (CRKP) strains and restricted therapeutic options pose a global threat to public health. Aminoglycosides are a wise choice, which can effectively reduce the mortality rate when combined with β-lactam drugs. However, in this study, we identified a ST15-KL112 CRKP FK3006 which not only exhibited resistance to carbapenems, but also exhibited high level resistance to aminoglycosides. In addition to the multidrug resistant phenotype, FK3006 also owned typical pathogenic characteristic, including hypermucoviscosity and hypervirulence phenotypes. According to the whole-genome sequencing, one pLVPK-like virulence plasmid, and three key resistant plasmids (<italic>bla</italic><sub>OXA-232</sub>, <italic>bla</italic><sub>CTX-M-15</sub>, and <italic>rmtF</italic>) were observed in FK3006. Compared to other typical ST15 CRKP, the presence of pLVPK-like virulence plasmid (p3006-2) endowed the FK3006 with high virulence features. High siderophore production, more cell invasive and more resistant to serum killing was observed in FK3006. The <italic>Galleria mellonella</italic> infection model also further confirmed the hypervirulent phenotype of FK3006 <italic>in vivo.</italic> Moreover, according to the conjugation assay, p3006-2 virulence plasmid also could be induced transfer with the help of conjugative IncFII<sub>K</sub> p3006-11 plasmid (<italic>bla</italic><sub>CTX-M-15</sub>). In addition to the transmissible plasmid, several insertion sequences and transposons were found around <italic>bla</italic><sub>CTX-M-15</sub>, and <italic>rmtF</italic> to generate the mobile antimicrobial resistance island (ARI), which also make a significant contribution to the dissemination of resistant determinants. Overall, we reported the uncommon co-existence of <italic>bla</italic><sub>OXA-232</sub>, <italic>rmtF</italic>-encoding plasmids, and pLVPK-like virulence plasmid in ST15-KL112 <italic>K. pneumoniae</italic>. The dissemination threatens of these high-risk elements in <italic>K. pneumoniae</italic> indicated that future studies are necessary to evaluate the prevalence of such isolates.</p>