2026-10-15T22:25:08Z https://data.mendeley.com/oai

oai:data.mendeley.com/45x4wyf96f.1 2021-03-18T15:42:09Z

Moya, Bartolome PDC-X producing PA isolates induction by AVI Mendeley Data Avibactam belongs to the new class of diazabicyclooctane β-lactamase inhibitors. Its inhibitory spectrum includes class A, C and D enzymes, including P. aeruginosa AmpC. Nonetheless, recent reports have revealed strain-dependent avibactam AmpC induction. In the present work, we wanted to assess the mechanistic basis underlying AmpC induction and determine if derepressed PDC-X mutated enzymes from ceftazidime/avibactam-resistant clinical isolates were further in-ducible. We determined avibactam concentrations that half-maximally inhibited (IC50) bocillin FL binding. Inducer β-lactams were also studied as comparators. Live cells’ time-course penicil-lin-binding proteins (PBPs) occupancy of avibactam was studied. To assess the ampC induction capacity of avibactam and comparators, qRT-PCR was performed in wild-type PAO1, PBP4, triple PBP4, 5/6 and 7 knockout derivatives and two ceftazidime/avibactam-susceptible/resistant XDR clinical isolates belonging to the epidemic high-risk clone ST175. PBP4 inhibition was observed for avibactam and β-lactam comparators. Induction capacity was consistently correlated with PBP4 binding affinity. Outer membrane permeability-limited PBP4 binding was observed in the live cells’ assay. As expected, imipenem and cefoxitin showed strong induction in PAO1, especially for carbapenem; avibactam induction was conversely weaker. Overall, the inducer effect was less remarkable in ampC-derepressed mutants and nonetheless absent upon avibactam exposure in the clinical isolates harboring mutated AmpC variants and their parental strains. Antimicrobial Resistance Beta-Lactamase Inhibitor Enzyme Induction Pseudomonas aeruginosa Lopez, Silvia Montaner, Maria Dataset doi:10.17632/45x4wyf96f.1 oai:data.mendeley.com/45x4wyf96f.1 Creative Commons Attribution 4.0 International http://creativecommons.org/licenses/by/4.0 https://data.mendeley.com/datasets/45x4wyf96f 2021-03-18T15:42:09Z