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Cellular small molecules are a major class of \u00b7NO\u2010reactive targets, possessing a variety of molecular functionalities that can react with \u00b7NO. Yet the capacity for secreted small molecules to react with \u00b7NO, as well as the biological consequences of such reactivity, have received little attention. Here, we explore the reactivity of \u00b7NO with phenazine metabolites, microbially\u2010derived secreted small molecules that possess antibiotic properties and can modulate their microenvironment. Using\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    <\/jats:styled-content>\n                    as a model phenazine producer, we find that \u00b7NO reacts with specific phenazines to yield stable, chemically distinct products. These chemical transformations significantly attenuate phenazine antibiotic properties, including against the phenazine nonproducer\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    , a competitor with\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                    <\/jats:styled-content>\n                    for niches in the context of infection. By contrast,\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                    <\/jats:styled-content>\n                    experiences rapid loss in viability when phenazines and \u00b7NO react. This toxicity occurs even in the presence of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>S. aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    , which displays resistance to nitrosylated phenazines, implicating a specific toxicity dependent on the formation of the phenazine\u2010NO adduct. These findings highlight the capacity of \u00b7NO to transform metabolite activity and suggest that \u00b7NO can tune microbial interactions in complex environments by a mechanism of action hitherto unappreciated.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70083","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:33:18Z","timestamp":1780986798000},"page":"145-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nitric Oxide Tunes Secreted Metabolite Bioactivity"],"prefix":"10.1111","volume":"126","author":[{"given":"Zachery R.","family":"Lonergan","sequence":"first","affiliation":[{"name":"Division of Biology and Biological Engineering California Institute of Technology  Pasadena California USA"},{"name":"Department of Biochemistry and Microbiology Rutgers University  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Weisflog","sequence":"additional","affiliation":[{"name":"Division of Biology and Biological Engineering California Institute of Technology  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Scurria","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biology and Biological Engineering California Institute of Technology  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korbinian","family":"Thalhammer","sequence":"additional","affiliation":[{"name":"Division of Geological and Planetary Sciences California Institute of Technology  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Conway","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1647-1918","authenticated-orcid":false,"given":"Dianne K.","family":"Newman","sequence":"additional","affiliation":[{"name":"Division of Biology and Biological Engineering California Institute of Technology  Pasadena California USA"},{"name":"Division of Geological and Planetary Sciences California Institute of Technology  Pasadena California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12650-2"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.6.3643"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303259"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.469990"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.8b01176"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci600404q"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.20.6.814"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9716997"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00779-06"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200612-1804OC"},{"key":"e_1_2_11_12_1","volume-title":"Sources of Nitric and Nitrous Acid in Grassland Soil","author":"Bisson G. 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