Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases in Enterobacteriaceae , Pseudomonas aeruginosa, and Acinetobacter baumannii | Zendy

Olga Lomovskaya | Zendy; Kirk Nelson | Zendy; Debora Rubio-Aparicio | Zendy; Ruslan Tsivkovski | Zendy; Dongxu Sun | Zendy; Michael N. Dudley | Zendy

Open Access

Impact of Intrinsic Resistance Mechanisms on Potency of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases in Enterobacteriaceae , Pseudomonas aeruginosa, and Acinetobacter baumannii

Author(s) -

Olga Lomovskaya,

Kirk Nelson,

Debora Rubio-Aparicio,

Ruslan Tsivkovski,

Dongxu Sun,

Michael N. Dudley

Publication year - 2020

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.00552-20

Subject(s) - acinetobacter baumannii , pseudomonas aeruginosa , microbiology and biotechnology , enterobacteriaceae , beta (programming language) , beta lactamase , potency , acinetobacter , beta lactamase inhibitors , beta lactam , klebsiella pneumoniae , antibiotic resistance , biology , antibiotics , escherichia coli , bacteria , in vitro , gene , genetics , computer science , programming language

QPX7728 is an ultrabroad-spectrum boronic acid beta-lactamase inhibitor that demonstrates inhibition of key serine and metallo-beta-lactamases at a nanomolar concentration range in biochemical assays with purified enzymes. The broad-spectrum inhibitory activity of QPX7728 observed in biochemical experiments translates into enhancement of the potency of many beta-lactams against strains of target pathogens producing beta-lactamases. The impacts of bacterial efflux and permeability on inhibitory potency were determined using isogenic panels of KPC-3-producing isogenic strains of Klebsiella pneumoniae and Pseudomonas aeruginosa and OXA-23-producing strains of Acinetobacter baumannii with various combinations of efflux and porin mutations.

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