Reduced catalytic activity of KPC β-lactamase can increase ceftazidime resistance
and shifts the rate-limiting step of catalysis to deacylation. Together, these mutations act cooperatively, reducing catalytic efficiency while promoting resistance to ceftazidime/avibactam. These findings reveal how epistatic interactions shape the evolution of clinically relevant β-lactamase variants and may help anticipate future resistance trajectories and guide inhibitor design.
Authors
- Murugesan Palaniappan (ORCID: https://orcid.org/0000-0003-4916-6565)
- Zhizeng Sun (ORCID: https://orcid.org/0000-0002-0033-5885)
- Devin Kelly
- Shahlo Solieva (ORCID: https://orcid.org/0000-0001-5350-2184)
- Timothy Palzkill
- Dignite Fabrice Ngango
- André Birgy
- Gregory Bowman
Institutions
- Inserm (FR)
- Baylor College of Medicine (US)
- Université Paris Cité (FR)
- University of Pennsylvania (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1038/s42003-026-09969-1
- Primary Topic
- Antibiotic Resistance in Bacteria
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases