Emergence of mcr-8.1-bearing MDR-hypervirulent Klebsiella pneumoniae ST307.

Abstract

We report for the first time whole-genome sequencing of four multidrug-resistant sequence type (ST) 307 Klebsiella pneumoniae recovered from patients in two hospitals in Armenia. Comparative genomic analysis revealed that the isolates were closely related, with a maximum of 39 single nucleotide polymorphism (SNP) differences in the core genome. All Armenian isolates carried the integrative and conjugative element ICEKp4, which bears the yersiniabactin locus, and shared a common evolutionary origin, diverging around 2005 (95% CI: 1999 to 2011). Antibiotic susceptibility testing showed resistance to several antibiotics, including ampicillin, amoxicillin-clavulanic acid, cefepime, ceftazidime, norfloxacin, levofloxacin, and chloramphenicol. Specifically, isolates designated as ARM03 and ARM06 were resistant to piperacillin-tazobactam, ARM04 and ARM05 had intermediate resistance to both piperacillin-tazobactam and imipenem, and ARM03 showed intermediate resistance to amikacin. We further identified antimicrobial resistance (AMR) genes in four Armenian isolates, including blaOXA-1, blaTEM-1D, blaSHV-28, dfrA14, tet(A), sul2, qnrB1, aac(6´)-Ib-cr, strA, strB and the extended-spectrum β-lactamase gene blaCTX-M-15. Additionally, ARM03 and ARM06 also obtained dfrA5, sul1, sul3, cmlA1, mphA, aph3-Ia and the unique colistin resistance gene mcr-8.1, which was absent in all other publicly available ST307 isolates. These two isolates also acquired aerobactin siderophore-encoding gene clusters (iucABCD-iutA) and the hypermucoidy locus rmpADC (ARM06 had rmpA fragment). ARM04 and ARM05, as well as ARM03 and ARM06, had nearly identical AMR and virulence genes, along with similar plasmid replicon profiles, respectively. Our findings suggest that a transmission event occurred between the two hospitals in Armenia, likely facilitated by patients or community members, during which K. pneumoniae ST307 isolates acquired plasmids carrying AMR and virulence genes.IMPORTANCEMultidrug-resistant (MDR) Klebsiella pneumoniae sequence type (ST) 307 has emerged as a high-risk clone associated with hospital- and community-acquired infections, posing a major threat to global public health. We report in-depth comparative genomics analyses of K. pneumoniae ST307 isolates recovered from patients in Armenia. The unique colistin resistance gene mcr-8.1 identified in ARM03 and ARM06 was absent in all other ST307 isolates obtained from the publicly available data sets. ARM03 and ARM06 also acquired aerobactin siderophore-encoding gene clusters (iucABCD-iutA) and the hypermucoidy locus rmpADC (ARM06 possessed incomplete rmpA fragment). Our findings suggest that a transmission event has occurred between two hospitals in Armenia either through patients or community members. In addition, the Armenian isolates obtained plasmids carrying virulence and AMR genes during the transmission event. Our study emphasises the importance of genomic surveillance of this emerging MDR-hypervirulent pathogen to provide early interventions.