AUTHOR=Prah Isaac , Nukui Yoko , Yamaoka Shoji , Saito Ryoichi 

TITLE=Emergence of a High-Risk Klebsiella michiganensis Clone Disseminating Carbapenemase Genes

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.880248

DOI=10.3389/fmicb.2022.880248

ISSN=1664-302X

ABSTRACT=<p><italic>Klebsiella michiganensis</italic> is emerging as an important human pathogen of concern especially strains with plasmid-mediated carbapenemase genes. The IncX3-<italic>bla</italic><sub>NDM-5</sub> plasmid has been described as the primary vector for <italic>bla</italic><sub>NDM-5</sub> dissemination. However, whether strains with this plasmid have any competitive edge remain largely unexplored. We characterized a <italic>bla</italic><sub>NDM-5</sub>-producing <italic>Klebsiella michiganensis</italic> strain (KO_408) from Japan and sought to understand the driving force behind the recent dissemination of IncX3-<italic>bl</italic>a<sub>NDM-5</sub> plasmids in different bacterial hosts. Antibiotic susceptibility testing, conjugation, and whole-genome sequencing were performed for KO_408, a clinical isolate recovered from a respiratory culture. Fitness, stability, and competitive assays were performed using the IncX3-<italic>bla</italic><sub>NDM-5</sub> plasmid, pKO_4-NDM-5. KO_408 was ascribed to a novel sequence type, ST256, and harbored resistance genes conforming to its MDR phenotype. The <italic>bla</italic><sub>NDM-5</sub> gene was localized on the ~44.9 kb IncX3 plasmid (pKO_4-NDM-5), which was transferable in the conjugal assay. The acquisition of pKO_4-NDM-5 did not impose any fitness burden and showed high stability in the host cells. However, transformants with pKO_4-NDM-5 were outcompeted by their host cells and transconjugants with the IncX3-<italic>bla</italic><sub>OXA-181</sub> plasmid. The genetic environment of <italic>bla</italic><sub>NDM-5</sub> in pKO_4-NDM-5 has been previously described. pKO_4-NDM-5 showed a close phylogenetic distance with seven similar plasmids from China. KO_408 clustered with strains within the KoI phylogroup, which is closely associated with carbapenemase genes. This study highlights the emergence of a high-risk <italic>Klebsiella michiganensis</italic> clone harboring carbapenemase genes and affirms that the recent spread of IncX3-<italic>bla</italic><sub>NDM-5</sub> plasmids might be due to their low fitness cost and stability but not their competitive prowess.</p>