Open AccessImpact 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 , klebsiella pneumoniae , microbiology and biotechnology , potency , efflux , biology , porin , beta lactamase inhibitors , enterobacteriaceae , serine , acinetobacter , enzyme , antibiotics , escherichia coli , bacteria , bacterial outer membrane , biochemistry , in vitro , gene , genetics
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.