CRISPRi screen identifies FprB as a synergistic target for gallium therapy in Pseudomonas aeruginosa.

ABSTRACT: With the rise of antibiotic-resistant bacteria, non-antibiotic therapies like gallium gain increasing attention. Intravenous gallium nitrate is under Phase II clinical trials to treat chronic Pseudomonas aeruginosa infections in cystic fibrosis patients. However, its clinical efficacy is constrained by the achievable peak concentration in human tissue. To address this limitation, we apply a genome-wide CRISPR interference approach (CRISPRi-seq) to identify potential synergistic targets with gallium. We classify the essential genes by response time and growth reduction, pinpointing the most vulnerable therapeutic targets in this species. In addition, we identify a highly conserved gene, fprB, encoding a ferredoxin-NADP⁺ reductase, whose deletion sensitizes P. aeruginosa to gallium, lowering

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12216716 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature