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

Background: The OXA-48-like enzymes are members of the class D β-lactamases, primarily detected in Enterobacterales, with the capacity to hydrolyze carbapenems. The allelic variant bla_OXA-163, which has low hydrolytic activity towards carbapenemes, was detected in Argentina in 2011 and spread successfully since then, giving sporadic origin to novel local variants.

Aim: To study the phenotypic profile and the dissemination strategies of two novel OXA enzymes, bla_OXA-438 and bla_OXA-567, harbored in Escherichia coli M17224 and Klebsiella pneumoniae M21014, isolated from two pediatric patients.

Methods: MICs were performed to determine the phenotypic profile of the clinical isolates, transcojugants 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 resistant to carbapenems and susceptible to ceftriaxone. bla_OXA-438 was located on an IncN₂ plasmid of 69 Kb while bla_OXA-567 on an IncC₂ plasmid of 175 Kb, both transferable by biparental conjugation. The close genetic environment of the bla_OXA genes suggests a common origin, likely involving mobile genetic elements. Finally, the clinical case of M21014 revealed previous infections of the patient with two genetically related K. pneumoniae ST6838, that carried bla_OXA-163 on IncC₂ plasmid with equal size and genetic hallmarks than that of M21014, providing strong evidence for the intrapatient emergence of bla_OXA-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.