OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From Escherichia coli

Abstract

OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative <i>Enterobacterales</i> worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical <i>E. coli</i> isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The <i>bla</i> _OXA _- ₄₈₄ was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring <i>bla</i> _OXA _- ₁₈₁. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10^-7 to 2.1 × 10^-6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as β-lactamase activity of OXA-232.