Deciphering the genetic context of the emerging OXA-484-producing carbapenem-resistant Escherichia coli from ST167 high-risk clone in the United Arab Emirates.

Abstract

Purpose: The evolution of new carbapenemase variants is alarming. We aimed to investigate the genetic context and molecular epidemiology of the emerging OXA-484 carbapenemase in the United Arab Emirates, to decipher its resistance mechanisms and evolutionary relationships.

Methods: Antimicrobial susceptibility testing was performed for an E. coli isolate recovered from an intrauterine contraceptive device of a patient returning to the UAE after a trip to Pakistan. Whole genome sequencing was used to characterize the genetic environment of bla_OXA-484, resistance and virulence determinants. Southern blotting was used to localize OXA-484 gene. Phylogenetic analysis established the sequence type (ST) and used to investigate relationships with global strains, and differences from other OXA-48-like types.

Results: The strain demonstrated selective resistance against ertapenem while maintaining susceptibility to imipenem and meropenem. OXA-484 exhibited R214G substitution affecting the enzyme's activity and distinguishing it from closely related variants like OXA-181 (214R) and OXA-232 (214 S). bla_OXA-484 was located on two non-conjugative plasmids (∼ 65 and 100 kb) within a genetic environment containing multiple insertion sequences. It belonged to the high-risk clone ST167, recognized for its enhanced capacity to acquire and maintain resistance determinants. The gene was mostly prevalent in the Western part of the world with limited distribution in the Middle East.

Conclusion: This study presents the first comprehensive characterization of OXA-484-producing E. coli ST167 in the UAE. The presence of bla_OXA-484 in high-risk clone warrants concern on its dissemination potential and underscores the importance of genomic surveillance and targeted infection control to prevent the spread of emerging resistance determinants.