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

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• OXA-48-like carbapenemases are prevalent in Gram-negative Enterobacterales globally, particularly in the Middle East, North Africa, and Europe.
• The emergence of new carbapenemase variants poses a significant threat to antimicrobial therapy.

Purpose of the Study:

• To characterize the novel carbapenemase OXA-484 from a clinical E. coli isolate.
• To investigate its antibiotic resistance profile, horizontal gene transfer capabilities, and genetic context.

Main Methods:

• Whole-genome sequencing and comparative analysis of the blaOXA-484 gene and its surrounding genetic elements.
• Determination of antibiotic resistance patterns through minimum inhibitory concentration (MIC) testing.
• Assessment of horizontal gene transfer (HGT) frequencies via conjugation experiments.

Main Results:

• OXA-484 differs from OXA-181 and OXA-232 by a single amino acid substitution (214G).
• The blaOXA-484 gene resides on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484), similar to plasmids carrying blaOXA-181.
• Low-frequency intraspecies and intergenus HGT of pOXA-484 was observed (1.4 × 10^-7 to 2.1 × 10^-6).
• OXA-484 conferred resistance to carbapenems and temocillin, with activity profiles intermediate between OXA-232/OXA-244 and OXA-48/OXA-181.

Conclusions:

• OXA-484 represents a new variant of OXA-48-like carbapenemases.
• It combines the plasmid support and transferability features of OXA-181-like enzymes with the beta-lactamase activity of OXA-232.
• This finding highlights the ongoing evolution and dissemination of carbapenem resistance mechanisms in Enterobacterales.