{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:13:33Z","timestamp":1784564013763,"version":"3.55.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T00:00:00Z","timestamp":1744588800000},"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. Parasitol."],"abstract":"<jats:p><jats:italic>Trichomonas vaginalis<\/jats:italic> is a flagellated protozoan causing trichomoniasis, the most common non-viral sexually transmitted infection. It is associated with various complications, particularly in asymptomatic carriers. Another major cause of vaginitis is <jats:italic>Candida albicans<\/jats:italic>, a normal member of the vaginal microbiota, which causes vulvovaginal candidiasis when immune imbalances occur, leading to recurrent infections. Treatment-resistant strains of these pathogens pose a significant challenge. <jats:italic>Lactobacillus crispatus<\/jats:italic>, a dominant species in the vaginal microbiota, produces antimicrobial compounds that help protect the vaginal mucosa. This study establishes an <jats:italic>in vitro<\/jats:italic> co-culture of <jats:italic>T. vaginalis<\/jats:italic>, <jats:italic>C. albicans<\/jats:italic>, and <jats:italic>L. crispatus<\/jats:italic> to simulate the vaginal microenvironment at the site of infection. MRS medium was chosen for the co-culture, with initial cell densities determined as follows: <jats:italic>T. vaginalis<\/jats:italic> at 1.0 \u00d7 10<jats:sup>6<\/jats:sup> trophozoites\/mL (counted using a hemocytometer), 3.33 \u00d7 10<jats:sup>4<\/jats:sup> CFU\/mL for <jats:italic>C. albicans<\/jats:italic>, and either 5.53 \u00d7 10<jats:sup>6<\/jats:sup> CFU\/mL (for co-culture with the ATCC isolate) or 5.53 \u00d7 10<jats:sup>7<\/jats:sup> CFU\/mL (for co-culture with a fresh clinical isolate) for <jats:italic>L. crispatus<\/jats:italic>. The cell densities of <jats:italic>C. albicans<\/jats:italic> and <jats:italic>L. crispatus<\/jats:italic> were quantified as colony-forming units (CFU) on selective agar. The incubation period for co-culture, ensuring optimal growth of all microorganisms, was 24 hours. In co-culture, <jats:italic>L. crispatus<\/jats:italic> at both tested densities acidified the medium. The co-culture system demonstrated lower MIC values for metronidazole (50 \u00b5M in the ATCC isolate co-culture and 25 \u00b5M with the fresh clinical isolate) and lower MFC values for fluconazole (6.25 \u00b5M), compared to monocultures of <jats:italic>T. vaginalis<\/jats:italic> (100 \u00b5M) and <jats:italic>C. albicans<\/jats:italic> (12.50 \u00b5M). Furthermore, the triple co-culture increased the cytotoxicity to vaginal cell and erythrocytes for the ATCC isolate while significantly inhibited both biofilm formation and metabolic activity of <jats:italic>C. albicans<\/jats:italic> (by up to 92% and 90%, respectively), as well as its yeast-to-hyphae transition (by up to 70%). SEM analyses highlighted the morphological differences among <jats:italic>T. vaginalis<\/jats:italic>, <jats:italic>C. albicans<\/jats:italic>, and <jats:italic>L. crispatus<\/jats:italic>, including isolate-specific size variations in the protozoan. These findings suggest that this <jats:italic>in vitro<\/jats:italic> co-culture system is a valuable tool for evaluating the antimicrobial efficacy of novel compounds against vaginitis pathogens and for studying interactions within the vaginal microenvironment.<\/jats:p>","DOI":"10.3389\/fpara.2025.1523113","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T01:17:53Z","timestamp":1744593473000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro co-culture model of Trichomonas vaginalis, Candida albicans, and Lactobacillus crispatus: a system for assessing antimicrobial activity and microorganism interactions in vaginitis"],"prefix":"10.3389","volume":"4","author":[{"given":"Fernanda Gomes","family":"Cardoso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Trindade dos","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saulo Almeida","family":"Menezes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziela Vargas","family":"Rigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiana","family":"Tasca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1093\/infdis\/171.5.1237","article-title":"Hemagglutination, adherence, and surface properties of vaginal Lactobacillus species","volume":"171","author":"Andreu","year":"1995","journal-title":"J. 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