{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:39Z","timestamp":1790920539548,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Candida albicans<\/jats:italic>\n is the predominant etiological agent of vulvovaginal candidiasis (VVC). Fluconazole (FLU), a first-line azole antifungal agent, has encountered growing resistance among vaginal isolates of\n C. albicans<\/jats:italic>\n due to prolonged, high-dose clinical administration. The development of such drug resistance arises from the synergistic interplay of multiple factors, with key mechanisms including enhanced biofilm formation, overexpression of drug efflux pump genes, and structural alterations in target enzymes driven by mutations in the\n ERG11<\/jats:italic>\n gene.\n Lactobacilli<\/jats:italic>\n , the dominant commensal probiotics in the vaginal microbiota, are known to inhibit biofilm formation by\n C. albicans<\/jats:italic>\n , a process closely linked to the development of antifungal resistance. Consequently, vaginal lactobacilli may serve as a pharmacological adjuvant to enhance the antifungal efficacy of fluconazole against\n C. albicans<\/jats:italic>\n . While existing research has primarily focused on the inhibitory effects of\n Lactobacilli<\/jats:italic>\n on\n C. albicans<\/jats:italic>\n proliferation, investigations into their impact on antifungal resistance remain limited.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We investigate the impact of vaginal\n L. paragasseri<\/jats:italic>\n on fluconazole-resistance phenotypes in a subset of clinical fluconazole-resistant\n C. albicans<\/jats:italic>\n isolates. Guided by established fluconazole-resistance mechanisms, we first screened fluconazole resistant\n C. albicans<\/jats:italic>\n isolates by assessing biofilm formation capacity, drug efflux pump gene expression, and\n ERG11<\/jats:italic>\n gene mutations and mRNA expression. Next, analysis of the vaginal\n Lactobacillus<\/jats:italic>\n composition in VVC patients and healthy controls showed a nominal, non-significant trend toward lower\n L. paragasseri<\/jats:italic>\n detection in VVC-affected women. Motivated by this trend and by prior evidence that\n Lactobacilli<\/jats:italic>\n can modulate antifungal-resistance phenotypes, we examined whether\n L. paragasseri<\/jats:italic>\n modulates fluconazole-resistance in clinically derived\n C. albicans<\/jats:italic>\n isolates through functional assays. Subsequent functional assessments, including standard antifungal susceptibility testing, biofilm formation assays, and drug efflux pump gene expression analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Vaginal\n L. paragasseri<\/jats:italic>\n can attenuate fluconazole-resistant phenotypes in the tested subset of clinical fluconazole-resistant\n C. albicans<\/jats:italic>\n isolates. In a murine vulvovaginal candidiasis model, adjunctive treatment with\n L. paragasseri<\/jats:italic>\n provided adjuvant benefit when added to fluconazole therapy, reducing vaginal\n C. albicans<\/jats:italic>\n colonization and alleviating infection-associated tissue damage. These in-vivo observations constitute preliminary pre-clinical evidence.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n These findings demonstrate that vaginal L. paragasseri holds promising potential as a probiotic adjunctive therapy for\n C. albicans<\/jats:italic>\n -induced VVC, offering novel insights for the development of alternative antifungal therapeutic strategies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1951876","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:37:17Z","timestamp":1790919437000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vaginal Lactobacillus paragasseri may attenuate fluconazole-resistant phenotypes in the subset of Candida albicans isolates and shows potential as a probiotic adjunct in antifungal therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiuyue","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Pan","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cui","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihai","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keran","family":"Jia","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukun","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Bethune International Peace Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2900","DOI":"10.1038\/s41598-019-39625-0","article-title":"Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG","volume":"9","author":"Allonsius","year":"2019","journal-title":"Sci. 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