• We characterized the features of 46 K. oxytoca complex isolates • We reveal the genetic determinants of resistance and cytotoxin production • Sequence type 176 emerged as a potential high-risk clone in this complex The Klebsiella oxytoca complex inhabits diverse environments, including the human gut, and frequently causes opportunistic infections. This species complex carries the intrinsic β-lactamase gene bla OXY , which confers resistance to ampicillin, and may acquire resistance to other antimicrobials, such as carbapenems, through mobile antimicrobial resistance genes or chromosomal mutations. A subset of the K. oxytoca complex produces cytotoxins associated with antibiotic-associated hemorrhagic colitis. However, the epidemiological and genomic data from Japan are limited. In this study, we aimed to characterize the genomic and phenotypic features of K. oxytoca complex collected nationwide in Japan within the scope of a national antimicrobial resistance surveillance (JARBS) program. A total of 46 K. oxytoca complex isolates were obtained through the JARBS program targeting third-generation cephalosporin-resistant and carbapenem-non-susceptible Enterobacterales in Japan. Whole-genome sequencing, antimicrobial susceptibility testing, plasmid analysis, and cell culture- and mass spectrometry-based cytotoxin detection were performed to investigate antimicrobial resistance and toxin production. Our analyses of clinical isolates revealed diverse genotypes and potential plasmid-mediated mechanisms for bla IMP acquisition. Phenotypic assays revealed multidrug resistance and cytotoxin production in a subset of isolates, and the corresponding genomic determinants were identified. Notably, we identified a multidrug-resistant, cytotoxin-producing lineage belonging to sequence type (ST) 176 that has disseminated across multiple regions of Japan. This study provides the first nationwide integrated genomic and phenotypic analysis of the K. oxytoca complex in Japan. The spread of the multidrug-resistant, cytotoxin-producing ST176 lineage represents a previously unrecognized high-risk linage in Japan, underscoring the need for continued genomic surveillance.
Sugawara et al. (Sun,) studied this question.