{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:20:35Z","timestamp":1793229635162,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFB3810200"],"award-info":[{"award-number":["2023YFB3810200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2010negative bacteria, including\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , develop resistance to ROS after six repeated exposures. Notably, ROS minimum inhibitory concentration of\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    significantly increases to 256\u2010fold after ten passages. The resistance mechanism predominantly originates from the intensified biosynthesis of the highly reductive hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) and pyoverdine (PVD) siderophores, effectively neutralizing ROS. Simultaneously, PVD transports Fe\n                    <jats:sup>3+<\/jats:sup>\n                    from the extracellular space into the bacteria, releasing H\n                    <jats:sub>2<\/jats:sub>\n                    S bound to Fe\n                    <jats:sup>3+<\/jats:sup>\n                    and enhancing ROS scavenging. Additionally, the enhanced outer membrane (OM) biogenesis establishes a robust OM barrier, impeding ROS penetration. The acquired resistance to ROS can be significantly reduced by incorporating additional Fe\n                    <jats:sup>3+<\/jats:sup>\n                    into the culture medium or disrupting the H\n                    <jats:sub>2<\/jats:sub>\n                    S biosynthetic gene. These observations suggest that careful consideration is required when utilizing ROS against Gram\u2010negative bacteria. It is anticipated that understanding this resistance mechanism can inform the development of future antimicrobial agents, particularly for Gram\u2010negative bacteria.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505748","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T10:25:57Z","timestamp":1757931957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Biosynthesis of H\n                    <sub>2<\/sub>\n                    S and Siderophores Targeting Gram\u2010Negative Bacterial Resistance to Reactive Oxygen Species"],"prefix":"10.1002","volume":"12","author":[{"given":"Congyang","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science and Health Engineering Hebei University of Technology  Xiping Avenue 5340, Beichen Tianjin 300401 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuilin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering Peking University  Beijing 100871 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M. C.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0887-088X","authenticated-orcid":false,"given":"Kelvin Wai Kwok","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics &amp; Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong  Pokfulam Hong Kong 999077 China"},{"name":"Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma Department of Orthopaedics and Traumatology The University of Hong Kong\u2010Shenzhen Hospital  Shenzhen 518053 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