Mutations in bla KPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases | Zendy

Ghady Haidar | Zendy; Cornelius J. Clancy | Zendy; Ryan K. Shields | Zendy; Binghua Hao | Zendy; Shaoji Cheng | Zendy; M. Hong Nguyen | Zendy

Open Access

Mutations in bla _KPC-3 That Confer Ceftazidime-Avibactam Resistance Encode Novel KPC-3 Variants That Function as Extended-Spectrum β-Lactamases

Author(s) -

Ghady Haidar,

Cornelius J. Clancy,

Ryan K. Shields,

Binghua Hao,

Shaoji Cheng,

M. Hong Nguyen

Publication year - 2017

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02534-16

Subject(s) - ceftazidime/avibactam , klebsiella pneumoniae , avibactam , ceftazidime , biology , mutant , mutagenesis , escherichia coli , genetics , microbiology and biotechnology , mutation , beta lactamase inhibitors , antibiotics , bacteria , gene , pseudomonas aeruginosa

We identified fourbla KPC-3 mutations in ceftazidime-avibactam-resistant clinicalKlebsiella pneumoniae isolates, corresponding to D179Y, T243M, D179Y/T243M, and EL165-166 KPC-3 variants. Using site-directed mutagenesis and transforming vectors intoEscherichia coli , we conclusively demonstrated that mutantbla KPC-3 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.

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