biostudies-literatureMao CNational Key R&D Program of ChinaNational Science Fund for Distinguished Youth ScholarGeneral Research Fund of Hong Kong Research Grant CouncilShenzhen Science and Technology FundingHong Kong Health and Medical Research FundNational Key Research and Development Program of Chinae05748https://www.ebi.ac.uk/biostudies/studies/S-EPMC12677624biostudies-literatureUnknown12(45)Reactive oxygen species (ROS) are a promising alternative bactericide. However, it is questioned that bacteria can potentially develop resistance to ROS, similar to their resistance against antibiotics and silver. Herein, it is reported that Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, develop resistance to ROS after six repeated exposures. Notably, ROS minimum inhibitory concentration of Pseudomonas aeruginosa significantly increases to 256-fold after ten passages. The resistance mechanism predominantly originates from the intensified biosynthesis of the highly reductive hydrogen sulfide (H₂S) and pyoverdine (PVD) siderophores, effectively neutralizing ROS. Simultaneously, PVD transports Fe³⁺ from the extracelAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Biosynthesis of H<sub>2</sub>S and Siderophores Targeting Gram-Negative Bacterial Resistance to Reactive Oxygen Species.PMC126776242120059223220952201904222322075251925104JCYJ2021032412001203422210832JCYJ20210324120009026171113222023YFB3810200Liu XQiao WWu JJin WMao CZhu YWu SXiang YCheung KMCYeung KWKfalseBiosynthesis of H<sub>2</sub>S and Siderophores Targeting Gram-Negative Bacterial Resistance to Reactive Oxygen Species.Reactive oxygen species (ROS) are a promising alternative bactericide. However, it is questioned that bacteria can potentially develop resistance to ROS, similar to their resistance against antibiotics and silver. Herein, it is reported that Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, develop resistance to ROS after six repeated exposures. Notably, ROS minimum inhibitory concentration of Pseudomonas aeruginosa significantly increases to 256-fold after ten passages. The resistance mechanism predominantly originates from the intensified biosynthesis of the highly reductive hydrogen sulfide (H₂S) and pyoverdine (PVD) siderophores, effectively neutralizing ROS. Simultaneously, PVD transports Fe³⁺ from the extracel2025-01-01T00:00:00Z2025 Dec2026-06-05T23:09:32.068Z2026-05-23T03:13:29.692ZS-EPMC126776244094836610.1002/advs.202505748