Mutations in genes <i>lpxL1</i>, <i>bamA</i>, and <i>pmrB</i> impair the susceptibility of cystic fibrosis strains of <i>Pseudomonas aeruginosa</i> to murepavadin.

ABSTRACT: Murepavadin is a peptidomimetic exhibiting specific inhibitory activity against Pseudomonas species. In the present study, its in vitro activity was assessed on 230 cystic fibrosis (CF) strains of Pseudomonas aeruginosa isolated from 12 French hospitals, in comparison with 12 other antipseudomonal antibiotics. Although murepavadin is still in preclinical stage of development, 9.1% (n = 21) of strains had a minimum inhibitory concentration (MIC) >4 mg/L, a level at least 128-fold higher than the modal MIC value of the whole collection (≤0.06 mg/L). Whole-genome sequencing of these 21 strains along with more susceptible isogenic counterparts coexisting in the same patients revealed diverse mutations in genes involved in the synthesis (lpxL1 and lpxL2

SUBMITTER: Ghassani A 

PROVIDER: S-EPMC10790571 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature