β-Lactamase Inhibitors Are Substrates for the Multidrug Efflux Pumps of Pseudomonas aeruginosa

• DOI: 10.1128/aac.42.2.399
• Publication Date: 2020-04-03T16:19:43Z
• Authors: Xian-Zhi Li; Li Zhang; Ramakrishnan Srik...; Keith Poole
• Keywords: Efflux; Cloxacillin; Beta-Lactamase Inhibitors; Pseudomonadales

The MexAB-OprM multidrug efflux system exports a number of antimicrobial compounds, including beta-lactams. In an attempt to define more fully the range compounds exported by this system, and, in particular, determine whether beta-lactamase inhibitors were also accommodated pump, influence pump status (its presence or absence) on intrinsic antibacterial activities these and their abilities enhance beta-lactam susceptibility intact cells was assessed. MIC determinations clearly demonstrated that all three tested, clavulanate, cloxacillin, BRL42715, pump. Moreover, using beta-lactams which readily hydrolyzed Pseudomonas aeruginosa class C chromosomal beta-lactamase, it elimination mexAB-oprM-encoded greatly enhanced cloxacillin BRL42715 (but not clavulanate) increase susceptibility. With poorly hydrolyzed, however, failed MexAB-OprM+ strains, although did MexAB-OprM- suggesting even with inhibitor effective when subjected efflux. MexEF-OprN-overexpressing but MexCD-OprJ-overexpressing facilitated resistance inhibitors, indicating are substrates for MexEF-OprN These data indicate ability inactivate (and like systems other bacteria) will markedly efficacies beta-lactam-beta-lactamase combinations treating bacterial infections.