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KPC Beta-Lactamases Are Permissive to Insertions and Deletions Conferring Substrate Spectrum Modifications and Resistance to Ceftazidime-Avibactam.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2020 Nov 17; Vol. 64 (12). Date of Electronic Publication: 2020 Nov 17 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- To explore the mutational possibilities of insertions and deletions (indels) in the Klebsiella pneumoniae carbapenemase (KPC) beta-lactamase, we selected for ceftazidime-avibactam-resistant mutants. Of 96 screened mutants, we obtained 19 indels (2 to 15 amino acids), all located in the loops surrounding the active site. Three antibiotic susceptibility phenotypes emerged: an extended-spectrum-beta-lactamase-like phenotype, an activity restricted to ceftazidime, and a carbapenem-susceptible KPC-like phenotype. Tolerance for indels reflects the evolvability of KPC beta-lactamase, which could challenge the therapeutic management of patients.<br /> (Copyright © 2020 American Society for Microbiology.)
- Subjects :
- Anti-Bacterial Agents pharmacology
Anti-Bacterial Agents therapeutic use
Bacterial Proteins genetics
Drug Combinations
Humans
Klebsiella pneumoniae genetics
Microbial Sensitivity Tests
beta-Lactamases genetics
Azabicyclo Compounds pharmacology
Ceftazidime pharmacology
Klebsiella Infections drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 64
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 33020157
- Full Text :
- https://doi.org/10.1128/AAC.01175-20