{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:41:38Z","timestamp":1785436898406,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Project Grants awarded by FEDER","award":["P20_00983"],"award-info":[{"award-number":["P20_00983"]}]},{"name":"UE","award":["PID2022-138870OB-I00\/AEI\/10.13039\/501100011033\/FEDER"],"award-info":[{"award-number":["PID2022-138870OB-I00\/AEI\/10.13039\/501100011033\/FEDER"]}]},{"name":"MICIU\/AEI","award":["RYC2023-043075-I"],"award-info":[{"award-number":["RYC2023-043075-I"]}]},{"DOI":"10.13039\/501100004895","name":"ESF+","doi-asserted-by":"crossref","award":["RYC2024-048202-I"],"award-info":[{"award-number":["RYC2024-048202-I"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RYC2024-048202-I"],"award-info":[{"award-number":["RYC2024-048202-I"]}],"id":[{"id":"https:\/\/ror.org\/04esata81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The emergence of multidrug-resistant Pseudomonas strains poses a serious threat to public health. Essential oil components, such as thymol (TH), exhibit potent antibacterial activity. However, the effects of continuous sublethal TH exposure and resulting changes to antibiotic susceptibility remain poorly understood. Here, we investigated a multi-resistant Pseudomonas psychrophila strain after TH adaptation using an integrated transcriptomic and metabolomic approach. Treatment with TH caused a significant decrease in MIC values for aminoglycosides (streptomycin, gentamicin, kanamycin) and tetracycline and increased susceptibility to five other antibiotics. Multi-omics analyses revealed coordinated changes in fatty acid metabolism (FabI downregulation and accumulation of unsaturated fatty acids), lipid A biosynthesis (LpxC downregulation), peptidoglycan synthesis (Mur genes downregulated, accompanied by increased spermine levels), and stress response pathways (such as GABA, GadA, maltose, and MalK). These results suggest that metabolic alterations and envelope remodeling potentially affect cell wall integrity and growth, which could, in turn, contribute to increased antibiotic susceptibility and re-sensitization. Overall, our findings highlight the potential of TH-mediated sensitization as a complementary strategy to restore antibiotic efficacy.<\/jats:p>","DOI":"10.3390\/ijms27093777","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"3777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Transcriptomics and Metabolomic Profiling Suggests That Thymol Adaptation Induces Multi-Layered Envelope and Metabolic Perturbations That Sensitize Pseudomonas psychrophila to Antibiotics"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-6726","authenticated-orcid":false,"given":"Natacha","family":"Caballero G\u00f3mez","sequence":"first","affiliation":[{"name":"Area of Microbiology, Department of Health Sciences, Faculty of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissal","family":"Naim","sequence":"additional","affiliation":[{"name":"Area of Microbiology, Department of Health Sciences, Faculty of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0787-1370","authenticated-orcid":false,"given":"Julia","family":"Manetsberger","sequence":"additional","affiliation":[{"name":"Area of Microbiology, Department of Health Sciences, Faculty of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7904-5081","authenticated-orcid":false,"given":"Carlos","family":"Terriente-Palacios","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Institute of Subtropical and Mediterranean Horticulture \u2018La Mayora\u2019, University of Malaga\u2014Consejo Superior de Investigaciones Cient\u00edficas (IHSM-UMA-CSIC), 29750 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-8706","authenticated-orcid":false,"given":"Jos\u00e9 G.","family":"Vallarino","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Institute of Subtropical and Mediterranean Horticulture \u2018La Mayora\u2019, University of Malaga\u2014Consejo Superior de Investigaciones Cient\u00edficas (IHSM-UMA-CSIC), 29750 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabil","family":"Benomar","sequence":"additional","affiliation":[{"name":"Area of Microbiology, Department of Health Sciences, Faculty of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0666-3978","authenticated-orcid":false,"given":"Hikmate","family":"Abriouel","sequence":"additional","affiliation":[{"name":"Area of Microbiology, Department of Health Sciences, Faculty of Health Sciences, University of Ja\u00e9n, 23071 Ja\u00e9n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s10096-015-2323-z","article-title":"Biofilm-specific antibiotic tolerance and resistance","volume":"34","author":"Olsen","year":"2015","journal-title":"Eur. 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