Novel allelic variants of blaOXA-48-like carried on IncN2 and IncC2 plasmids isolated from clinical cases in Argentina: In vivo emergence of blaOXA-567

Abstract

ABSTRACT: Objective: The OXA-48-like enzymes have the capacity to hydrolyse carbapenems and are members of class D β-lactamases that are primarily detected in Enterobacterales. The allelic variant blaOXA-163, which has low hydrolytic activity towards carbapenems, was detected in Argentina in 2011 and has spread successfully since then, giving sporadic origin to novel local variants. The aim of this study was to analyse the phenotypic profile and dissemination strategies of two novel OXA enzymes, blaOXA-438 and blaOXA-567, located in Escherichia coli M17224 and Klebsiella pneumoniae M21014, respectively, isolated from two paediatric patients. Methods: Minimum inhibitory concentration measurements were performed to determine the phenotypic profile of the clinical isolates, transconjugants and transformant cells. Biparental conjugation, PCR, Sanger and whole-genome sequencing were performed to determine the complete genetic characteristics of the plasmids. Results: Both isolates were found to be resistant to carbapenems and susceptible to ceftriaxone. blaOXA-438 was located on a 69-kb IncN2 plasmid, while blaOXA-567 was found on a 175-Kb IncC2 plasmid, both transferable by biparental conjugation. The close genetic environment of the blaOXA genes suggests a common origin likely involving mobile genetic elements. Finally, the clinical case of M21014 revealed that the patient had previous infections with two genetically related K. pneumoniae ST6838 that carried blaOXA-163 on an IncC2 plasmid with equal size and genetic hallmarks to that of M21014, providing strong evidence for the intra-patient emergence of blaOXA-567. Conclusions: This research underscores the need for ongoing surveillance and integral studies to understand the emergence, biochemistry and dissemination capacity of OXA enzymes with the overarching aim to halt their spread.

Keywords

• OXA-48-like
• OXA-163
• Carbapenemase
• IncN
• IncC
• Plasmid