Abstract
Pseudomonas aeruginosa (P. aeruginosa) biofilms pose substantial challenges in clinical settings due to their resistance to conventional antibiotic treatments. This study investigated the influence of reductive stress on the formation and eradication of P. aeruginosa biofilms. A series of redox-active compounds were employed to assess their impact on both biofilm development and disruption. Among them, hydrazine (HZ) showed potent activity. Mechanistic studies revealed that these compounds suppressed pyocyanin production and impaired bacterial metabolic activity. A structure-activity relationship analysis highlighted hydroxylamine (HA) as a promising candidate, owing to its favorable balance between efficacy and cytotoxicity. Notably, quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis of HA-treated P. aeruginosa suggested inhibition of matrix biosynthesis, quorum sensing, and oxidative stress defenses. This study provides insights into biofilm management by targeting the redox environment, offering potential strategies for the development of redox-based therapies to combat biofilm-associated infections.