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Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam

  • Melina Ruggiero1,2
  • Melina García Alonso1
  • Salvador I. Drusin3,4
  • Roque Figueroa-Espinosa1
  • Ivan Jackson Briceño Muñoz1
  • Robert A. Bonomo5,6,7,8,9,10,11,12
  • Gabriel Gutkind1,2
  • José Di Conza1,2
  • Diego M. Moreno3,4
  • Pablo Power1,2
12 affiliations
  1. 1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Investigaciones en Bacteriología y Virología Molecular (IBaViM), Buenos Aires, Argentina
  2. 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
  3. 3IQUIR (Instituto de Química Rosario), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
  4. 4Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Argentina
  5. 5Medical Service, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
  6. 6GRECC, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
  7. 7Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  8. 8Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  9. 9Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  10. 10Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  11. 11Department of Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
  12. 12CWRU-Cleveland VAMC Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Cleveland, Ohio, USA
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Abstract

PER-1-producing Pseudomonas and Acinetobacter and PER-2-producing Enterobacterales, respectively, are increasingly difficult to treat due to combined resistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Through combined functional and in silico analyses, we demonstrated that PER-14 is resistant to avibactam and relebactam inhibition while retaining an extended-spectrum activity and the ability to hydrolyze cefiderocol, as the S130T substitution affects the proper binding of the DBOs.

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Cite

BibTeXRIS
BibTeX
@article{ruggiero2026per14,
  title = {{PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam}},
  author = {Melina Ruggiero and Melina García Alonso and Salvador I. Drusin and Roque Figueroa-Espinosa and Ivan Jackson Briceño Muñoz and Robert A. Bonomo and Gabriel Gutkind and José Di Conza and Diego M. Moreno and Pablo Power},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = jul,
  doi = {10.1128/aac.00378-26},
  url = {https://doi.org/10.1128/aac.00378-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - PER-14, a β-lactamase variant with reduced sensitivity to avibactam and relebactam
AU  - Melina Ruggiero
AU  - Melina García Alonso
AU  - Salvador I. Drusin
AU  - Roque Figueroa-Espinosa
AU  - Ivan Jackson Briceño Muñoz
AU  - Robert A. Bonomo
AU  - Gabriel Gutkind
AU  - José Di Conza
AU  - Diego M. Moreno
AU  - Pablo Power
PY  - 2026
DA  - 2026/07/21
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00378-26
UR  - https://doi.org/10.1128/aac.00378-26
AB  - PER-1-producing Pseudomonas and Acinetobacter and PER-2-producing Enterobacterales, respectively, are increasingly difficult to treat due to combined resistance to antibiotics like ceftazidime, cefiderocol, and ceftazidime/aztreonam-avibactam, among others. PER-14 differs from PER-2 by an S130T substitution. Through combined functional and in silico analyses, we demonstrated that PER-14 is resistant to avibactam and relebactam inhibition while retaining an extended-spectrum activity and the ability to hydrolyze cefiderocol, as the S130T substitution affects the proper binding of the DBOs.
SN  - 0066-4804
SN  - 1098-6596
ER  -