赋予头孢他啶-阿维巴坦耐药性的突变编码新型KPC-3变体，其作为超广谱β-内酰胺酶发挥作用。
Mutations in That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases.
作者信息
Haidar Ghady, Clancy Cornelius J, Shields Ryan K, Hao Binghua, Cheng Shaoji, Nguyen M Hong
机构信息
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
出版信息
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02534-16. Print 2017 May.
Abstract
We identified four mutations in ceftazidime-avibactam-resistant clinical isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors into , we conclusively demonstrated that mutant encoded enzymes that functioned as extended-spectrum β-lactamases; mutations directly conferred higher MICs of ceftazidime-avibactam and decreased the MICs of carbapenems and other β-lactams. Impact was strongest for the D179Y mutant, highlighting the importance of the KPC Ω-loop.
摘要
我们在对头孢他啶-阿维巴坦耐药的临床分离株中鉴定出四种突变，分别对应于D179Y、T243M、D179Y/T243M和EL165 - 166 KPC - 3变体。通过定点诱变并将载体转化入……，我们最终证明突变体编码的酶发挥超广谱β-内酰胺酶的作用；这些突变直接导致头孢他啶-阿维巴坦的最低抑菌浓度（MIC）升高，并降低了碳青霉烯类和其他β-内酰胺类药物的MIC。对D179Y突变体的影响最为显著，突出了KPC Ω环的重要性。
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