Differential contribution of PBP occupancy and efflux on the effectiveness of β-lactams at their target site in clinical isolates of Neisseria gonorrhoeae.

ABSTRACT: Neisseria gonorrhoeae exhibits alarming antibiotic resistance trends and poses a significant challenge in therapeutic management. This study aimed to explore the association of penA alleles with penicillin-binding protein (PBP) occupancy patterns and reduced outer membrane permeability, impacting susceptibility to last-line cephalosporins and potential β-lactam candidates. The whole genome sequence, the MICs and PBP IC50s were determined for 12 β-lactams and β-lactamase inhibitors in 8 clinical isolates with varying β-lactam sensitivity, 2 ATCC, and 3 WHO cephalosporin-resistant reference strains. The genetic analysis identified diverse determinants of β-lactam resistance including penA, ponA, porB, and mtrR alterations. Mosaic penA alleles were confirmed to be key determinants of cephalos

SUBMITTER: Lopez-Arguello S 

PROVIDER: S-EPMC11729944 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature