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PreprintCC BY-NDbioRxiv

Phenotypic Characterization of OXA-439, an OXA-163 variant, isolated from uropathogenic Escherichia coli

  1. 1Institut Pasteur de Montevideo

Abstract

OXA-48-like {beta}-lactamases, such as OXA-163, OXA-181, OXA-405, OXA-505, among others, are class D carbapenem-hydrolyzing enzymes increasingly reported worldwide, yet some variants remain poorly characterized at the phenotypic levels. Here, we report OXA-439, a variant of OXA-163, in a producing uropathogenic Escherichia coli (UPEC) in Uruguay, recovered from a catheter-associated urinary tract infection with discordant routine susceptibility results. The specific contribution of OXA-439, bla-OXA-48, bla-OXA-163, and bla-OXA-439 were cloned into pET24a vector and expressed in Escherichia coli BL21(DE3), and their activity was evaluated by MIC microdilution against a panel of penicillins, ESCs, carbapenems, and {beta}-lactam/{beta}-lactamase inhibitor combinations. OXA-439 exhibited a substrate profile highly similar to OXA-163 conferring resistance to piperacillin and third-generation cephalosporins while remaining susceptible to carbapenems but with globally reduced MIC values and a complete loss of activity toward amoxicillin and clavulanate. These data suggest that the Y123H substitution, located near the catalytic Ser70/Lys73 region, subtly perturbs the active-site environment and decreases penicillinase efficiency.

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BibTeX
@misc{florezcardona2026phenotypic,
  title = {{Phenotypic Characterization of OXA-439, an OXA-163 variant, isolated from uropathogenic Escherichia coli}},
  author = {V. Florez-Cardona and E. Ticona-Morales and M. Charlo and B. Manta},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.12.751137},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.12.751137v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - Phenotypic Characterization of OXA-439, an OXA-163 variant, isolated from uropathogenic Escherichia coli
AU  - V. Florez-Cardona
AU  - E. Ticona-Morales
AU  - M. Charlo
AU  - B. Manta
PY  - 2026
DA  - 2026/09/12
PB  - bioRxiv
DO  - 10.64898/2026.09.12.751137
UR  - https://www.biorxiv.org/content/10.64898/2026.09.12.751137v1
AB  - OXA-48-like {beta}-lactamases, such as OXA-163, OXA-181, OXA-405, OXA-505, among others, are class D carbapenem-hydrolyzing enzymes increasingly reported worldwide, yet some variants remain poorly characterized at the phenotypic levels. Here, we report OXA-439, a variant of OXA-163, in a producing uropathogenic Escherichia coli (UPEC) in Uruguay, recovered from a catheter-associated urinary tract infection with discordant routine susceptibility results. The specific contribution of OXA-439, bla-OXA-48, bla-OXA-163, and bla-OXA-439 were cloned into pET24a vector and expressed in Escherichia coli BL21(DE3), and their activity was evaluated by MIC microdilution against a panel of penicillins, ESCs, carbapenems, and {beta}-lactam/{beta}-lactamase inhibitor combinations. OXA-439 exhibited a substrate profile highly similar to OXA-163 conferring resistance to piperacillin and third-generation cephalosporins while remaining susceptible to carbapenems but with globally reduced MIC values and a complete loss of activity toward amoxicillin and clavulanate. These data suggest that the Y123H substitution, located near the catalytic Ser70/Lys73 region, subtly perturbs the active-site environment and decreases penicillinase efficiency.
ER  -