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In this study, we investigated the impact of cell-free supernatant (CFS) from human vaginal\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    spp. on the formation of\n                    <jats:italic>E. coli<\/jats:italic>\n                    UTI89 persister cells. Among various antibiotics tested, colistin exposure resulted in the highest percentage of persister cells, followed by meropenem, with ampicillin showing the least effect. Fractionation of the CFS via column chromatography yielded seven fractions, with fractions C4 and C7 demonstrating a synergistic inhibition of\n                    <jats:italic>E. coli<\/jats:italic>\n                    persisters. Gas chromatography-mass spectrometry (GC-MS) identified itaconic anhydride and (-)-terpinen-4-ol as the key metabolites responsible for this effect. When combined with colistin and meropenem, these compounds (8\u00a0\u00b5g\/ml and 5\u00a0\u00b5g\/ml, respectively) significantly reduced persister cell formation. The bactericidal action was found to be ROS-dependent, as evidenced by the reduced efficacy in the presence of thiourea, a hydroxyl radical scavenger. Additionally, these metabolites increased membrane permeability and inhibited efflux pumps, further enhancing antibiotic efficacy. Building on these findings, we developed a novel postbiotic-based vaginal wash formulation incorporating (-)-terpinen-4-ol, itaconic anhydride, and tryptamine, another metabolite with antibiofilm properties. These bioactive compounds, isolated from indigenous human vaginal\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    spp., were incorporated into a poloxamer 407-based formulation designed to prevent urinary tract infections (UTIs) and combat antimicrobial resistance. Preclinical studies conducted on BALB\/c mice models validated the formulation\u2019s efficacy and safety, highlighting its potential for clinical translation. This approach of combining the antipersister, efflux inhibitory, and antibiofilm activities of these postbiotics within a practical therapeutic formulation offers a promising strategy for improving UTI management and combating the growing challenge of antibiotic tolerance.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-35736-7","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T06:44:41Z","timestamp":1768027481000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synergistic antipersister, efflux inhibitory &amp; antibiofilm activities of vaginal Lactobacillus-derived postbiotics against UPEC: toward a novel therapeutic for utis"],"prefix":"10.1038","volume":"16","author":[{"given":"Veena G.","family":"Nair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Raj","family":"Chellappan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramya Devi","family":"Durai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Y.B.R.D","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhiviya","family":"Narbhavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupriya","family":"A.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhusaran","family":"N.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saisubramanian","family":"Nagarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"35736_CR1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1086\/318850","volume":"183","author":"WE Stamm","year":"2001","unstructured":"Stamm, W. 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Cranberry-derived bioactives for the prevention and treatment of urinary tract infections: antimicrobial mechanisms and global research trends in nutraceutical applications. Front Nutr 12, 1502720 (2025).","DOI":"10.3389\/fnut.2025.1502720"},{"key":"35736_CR56","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3390\/antibiotics14070634","volume":"14","author":"BY Chen","year":"2025","unstructured":"Chen, B. Y., Liu, Z. S., Lin, Y. S., Lin, H. C. & Chen, P. W. Oral administration of Heat-Killed Multi-Strain probiotics confers durable protection against Antibiotic-Resistant primary and recurrent urinary tract infections in a murine model. Antibiotics 14, 634 (2025).","journal-title":"Antibiotics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35736-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35736-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35736-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:03:14Z","timestamp":1770332594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35736-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,10]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["35736"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-35736-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-8039921\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,10]]},"assertion":[{"value":"5 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors have filed an Indian patent for a formulation containing postbiotics derived from Lactobacilli to treat induced urinary tract infections in a mouse model (Patent Application Number: 202441057663; Reference Number: TEMP\/E-1\/67129\/2024-CHE).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal experiments were approved by the\n                      Institutional Animal Ethics Committee (IAEC)\n                      ,\n                      SASTRA Deemed to be University\n                      (Approval No.\n                      740\/SASTRA\/IAEC\/RPP\n                      ). The animal studies were conducted in accordance with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India. The animal experiments reported were performed in accordance with ARRIVE guidelines. All animals used in this study were procured, housed, and maintained at the Central Animal House Facility, SASTRA Deemed to be University. Animals were kept under standard laboratory conditions with controlled temperature, humidity, and a 12\u00a0h light\/dark cycle, with ad libitum access to standard pellet diet and water. Following experimental infection, animals received intravaginal treatment with the respective formulations as described in the Methods section.Human ethical approval for the collection of human vaginal samples for this study was granted by the\n                      Institutional Ethics Committee\n                      ,\n                      Trichy SRM Medical College and Research Centre (TSRMMCH&RC)\n                      ,\n                      Tiruchirappalli\n                      ,\n                      Tamil Nadu\n                      ,\n                      India\n                      (IEC No. 127, 696\/TSRMMCH&RC\/ME-1\/2022). Written informed consent was obtained from all participants before sample collection.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical declaration"}}],"article-number":"5005"}}