KPC β-内酰胺酶允许插入和缺失，从而导致底物谱的修饰和对头孢他啶-阿维巴坦的耐药性。
KPC Beta-Lactamases Are Permissive to Insertions and Deletions Conferring Substrate Spectrum Modifications and Resistance to Ceftazidime-Avibactam.
机构信息
IAME, UMR 1137, INSERM, Université de Paris, AP-HP, Paris, France.
Laboratoire de Microbiologie, Hôpital Robert Debré, AP-HP, Paris, France.
出版信息
Antimicrob Agents Chemother. 2020 Nov 17;64(12). doi: 10.1128/AAC.01175-20.
Abstract
To explore the mutational possibilities of insertions and deletions (indels) in the 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.
摘要
为了探索碳青霉烯酶（KPC）β-内酰胺酶插入和缺失（indels）的突变可能性，我们选择了对头孢他啶-阿维巴坦耐药的突变体。在筛选的 96 个突变体中，我们获得了 19 个 indels（2 到 15 个氨基酸），它们都位于活性位点周围的环中。出现了三种抗生素敏感性表型：一种类似于扩展谱β-内酰胺酶的表型，一种仅限于头孢他啶的活性，以及一种对碳青霉烯类敏感的类似于 KPC 的表型。对 indels 的耐受性反映了 KPC β-内酰胺酶的可进化性，这可能会对患者的治疗管理构成挑战。
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