期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 12, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01175-20
关键词
KPC; carbapenemase; ceftazidime-avibactam; deletion; hydrolysis spectrum; insertion; mutation; mutational tolerance; omega loop
资金
- Fondation ARC pour la Recherche sur le Cancer [DOC20190509066]
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.
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