{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:16:31Z","timestamp":1788171391947,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Human Capacity Development Program of the Kurdistan Regional Government, Iraq."},{"id":[{"id":"https:\/\/ror.org\/05g801a49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Carbon monoxide-releasing molecules (CORMs) display promising antibacterial activity, yet their global cellular targets and underlying mechanisms remain incompletely understood. This study aimed to characterize the proteomic response of Escherichia coli MG1655 exposed to a sub-inhibitory concentration (10 \u00b5M, 40 min) of the ruthenium-based CORM-3 compared to its inactive counterpart, iCORM-3, in defined minimal medium. Utilizing label-free quantitative LC-MS\/MS proteomics combined with differential abundance, functional annotation, and STRING-based network analyses, we explored treatment-associated proteomic signatures and subcellular localization patterns. While iCORM-3 exhibited no antibacterial activity, CORM-3 inhibited growth in a concentration-dependent manner. Although no individual protein reached FDR significance after multiple-testing correction, candidate abundance changes converged on functionally related modules, including envelope\/periplasmic stress, sulfur metabolism and transport, redox\/metal homeostasis and selected energy-associated functions. These findings support a hypothesis-generating model in which sub-inhibitory CORM-3 exposure is associated with multifactorial bacterial stress adaptation rather than a single dominant protein-level target. Envelope homeostasis, sulfur-containing pathways, redox\/metal adaptation, and attenuation of selected energy-associated functions therefore emerge as candidate components of the E. coli response to CORM-3 and require future targeted validation.<\/jats:p>","DOI":"10.3390\/microorganisms14091918","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:21:19Z","timestamp":1788168079000},"page":"1918","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory Label-Free Proteomic Profiling of the Escherichia coli Response to Sub-Inhibitory CORM-3 Exposure"],"prefix":"10.3390","volume":"14","author":[{"given":"Salar","family":"Ali","sequence":"first","affiliation":[{"name":"College of Health and Medical Technology, Sulaimani Polytechnic University, Sulaimani 46001, Iraq"},{"name":"Nursing Department, Kurdistan Technical Institute, Sulaimani 46001, Iraq"},{"name":"Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-8931","authenticated-orcid":false,"given":"Salvatore","family":"Dimonte","sequence":"additional","affiliation":[{"name":"BioMolecular Lab, 76121 Barletta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8417-2103","authenticated-orcid":false,"given":"Stefano","family":"Aquaro","sequence":"additional","affiliation":[{"name":"Department of Life, Health and Environmental Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Muhammed","family":"Babakir-Mina","sequence":"additional","affiliation":[{"name":"College of Health and Medical Technology, Sulaimani Polytechnic University, Sulaimani 46001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5850-2810","authenticated-orcid":false,"given":"Giovanni","family":"Di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral, and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6309-6981","authenticated-orcid":false,"given":"Arianna","family":"Pompilio","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral, and Biotechnological Sciences, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"},{"name":"Center for Advanced Studies and Technology (CAST), \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1034\/j.1600-0773.2003.930306.x","article-title":"Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain","volume":"93","author":"Alonso","year":"2003","journal-title":"Pharmacol. 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