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.

中文翻译：

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KPC Beta-内酰胺酶允许插入和缺失，赋予底物光谱修饰和对头孢他啶-阿维巴坦的抗性

为了探索在肺炎克雷伯氏菌碳青霉烯酶（KPC）β-内酰胺酶中插入和缺失（indels）的突变可能性，我们选择了对头孢他啶-avibactam具有抗性的突变体。在96个筛选的突变体中，我们获得了19个插入缺失（2至15个氨基酸），全部位于活性位点周围的环中。出现了三种抗生素敏感性表型：一种广谱的β-内酰胺酶样表型，一种限制于头孢他啶的活性，以及​​一种对碳青霉烯敏感的KPC样表型。插入缺失的耐受性反映了KPCβ-内酰胺酶的进化能力，这可能会挑战患者的治疗管理。