{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:51:07Z","timestamp":1791823867050,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T00:00:00Z","timestamp":1716768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010270","name":"Capital Health Research and Development of Special","doi-asserted-by":"publisher","award":["2024-1-2241"],"award-info":[{"award-number":["2024-1-2241"]}],"id":[{"id":"10.13039\/501100010270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["61927819"],"award-info":[{"award-number":["61927819"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vaginitis is a common infection in women, with approximately 75% of women experiencing at least one episode during their lifetime. Although antimicrobial agents are widely used to treat vaginitis, recurrent vaginitis occurs in some patients. Resistance to these agents is the major cause of recurrent vaginitis. Therefore, there is an urgent need to develop novel drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the efficacy of a new biological bacteriostatic agent (BBA), composed of lysozyme, phytoalexin, chitosan oligosaccharide, sinensetin, 18\u03b2\/20\u03b1-glycyrrhizin, and betaine, against vaginitis using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> studies. First, we evaluated the antibacterial effects of BBA against 13 microbial strains commonly present in aerobic vaginitis, bacterial vaginosis, vulvovaginal candidiasis, and healthy vaginas. Second, we assessed the safety of various doses of BBA administered orally for 4\u2009weeks in female mice. Third, we examined the <jats:italic>in vivo<\/jats:italic> anti-proliferative and anti-inflammatory effects of BBA in <jats:italic>Candida albicans-<\/jats:italic>, <jats:italic>Candida glabrata<\/jats:italic>-, and <jats:italic>Gardnerella<\/jats:italic>-induced vaginitis models. Finally, we evaluated the anti-vaginitis effect of a BBA gel prepared with 0.5% (w\/v) ammonium acryloyldimethyltaurate\/Vp copolymer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BBA effectively suppressed the growth of the main causative pathogens of vaginitis <jats:italic>in vitro<\/jats:italic>. BBA, either undiluted or diluted two-fold, inhibited all microorganisms cultured for 8\u2009h. No obvious organ damage was detected when BBA was administered to mice. Both BBA alone and 70% BBA in a gel formulation effectively inhibited the proliferation of <jats:italic>C. albicans<\/jats:italic>, <jats:italic>C. glabrata<\/jats:italic>, and <jats:italic>Gardnerella<\/jats:italic> in vaginal lavage samples and alleviated tissue inflammation in mice with vaginitis. The 70% BBA gel performed better than BBA alone at treating vaginitis in mice infected with <jats:italic>Gardnerella vaginalis<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BBA alone and a 70% BBA gel inhibited the growth of pathogens and effectively alleviated inflammation caused by <jats:italic>C. albicans<\/jats:italic>, <jats:italic>C. glabrata<\/jats:italic>, and <jats:italic>G. vaginalis<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1341878","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T04:11:27Z","timestamp":1716783087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A non-antibiotic antimicrobial drug, a biological bacteriostatic agent, is useful for treating aerobic vaginitis, bacterial vaginosis, and vulvovaginal candidiasis"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhen","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinping","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojia","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0263522","DOI":"10.1371\/journal.pone.0263522","article-title":"Prevalence of biofilms in Candida spp. bloodstream infections: a meta-analysis","volume":"17","author":"Atiencia-Carrera","year":"2022","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"960","DOI":"10.3923\/pjbs.2011.960.966","article-title":"A comprehensive review of vaginitis phytotherapy","volume":"14","author":"Azimi","year":"2011","journal-title":"Pak. J. Biol. Sci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1093\/infdis\/jiw159","article-title":"Current treatment of bacterial vaginosis-limitations and need for innovation","volume":"214","author":"Bradshaw","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.2217\/fmb-2018-0299","article-title":"Candida albicans vaginitis in a murine model is reduced by polypeptide-enriched Gastrodia elata extracts","volume":"14","author":"Cai","year":"2019","journal-title":"Future Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12934-020-01464-4","article-title":"Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health","volume":"19","author":"Chee","year":"2020","journal-title":"Microb. Cell Factories"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1119312","DOI":"10.3389\/fvets.2023.1119312","article-title":"Reproduction and viscera organ characteristics of MSTN and FGF5 dual-gene knockout sheep","volume":"10","author":"Chen","year":"2023","journal-title":"Front. Vet. Sci."},{"key":"ref7","volume-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically","author":"Cockerill","year":"2012"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2006.03.012","article-title":"Gels as vaginal drug delivery systems","volume":"318","author":"das Neves","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1111\/j.1471-0528.2009.02237.x","article-title":"Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy","volume":"116","author":"Donders","year":"2009","journal-title":"BJOG"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s00404-012-2571-4","article-title":"Aerobic vaginitis and mixed infections: comparison of clinical and laboratory findings","volume":"287","author":"Fan","year":"2013","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1093\/infdis\/jiy704","article-title":"Gardnerella vaginalis and Prevotella bivia trigger distinct and overlapping phenotypes in a mouse model of bacterial vaginosis","volume":"220","author":"Gilbert","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"4540","DOI":"10.1128\/AAC.00565-09","article-title":"Efficacy of albaconazole against Candida albicans in a vaginitis model","volume":"53","author":"Gonz\u00e1lez","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e1270","DOI":"10.31661\/gmj.v8i0.1270","article-title":"An evidence-based review of medicinal plants used for the treatment of vaginitis by Avicenna in \"the canon of medicine\"","volume":"8","author":"Khalilzadeh","year":"2019","journal-title":"Galen Med. J."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1038\/s41591-019-0600-6","article-title":"Vaginal microbiome transplantation in women with intractable bacterial vaginosis","volume":"25","author":"Lev-Sagie","year":"2019","journal-title":"Nat. Med."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e2200363","DOI":"10.1002\/mnfr.202200363","article-title":"Protocatechuic acid delays postovulatory oocyte ageing in mouse","volume":"67","author":"Li","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s40168-023-01497-y","article-title":"Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice","volume":"11","author":"Li","year":"2023","journal-title":"Microbiome"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.3892\/etm.2019.7772","article-title":"Berberine exhibits antioxidative effects and reduces apoptosis of the vaginal epithelium in bacterial vaginosis","volume":"18","author":"Ma","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1093\/infdis\/jiv338","article-title":"Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis","volume":"212","author":"Machado","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"976057","DOI":"10.3389\/fcimb.2022.976057","article-title":"Editorial: vaginal dysbiosis and biofilms","volume":"12","author":"Machado","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.mayocp.2021.09.022","article-title":"Evaluation and Management of Vaginitis","volume":"97","author":"Marnach","year":"2022","journal-title":"Mayo Clin. Proc."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1097\/OLQ.0000000000000298","article-title":"Hydrogen peroxide-producing lactobacilli are associated with lower levels of vaginal interleukin-1beta, independent of bacterial vaginosis","volume":"42","author":"Mitchell","year":"2015","journal-title":"Sex. Transm. Dis."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40168-016-0203-0","article-title":"The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next?","volume":"4","author":"Mitra","year":"2016","journal-title":"Microbiome"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"978","DOI":"10.3390\/antibiotics10080978","article-title":"Comparative effectiveness of treatments for bacterial vaginosis: a network meta-analysis","volume":"10","author":"Mu\u00f1oz-Barreno","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"863208","DOI":"10.3389\/fcimb.2022.863208","article-title":"Clustering analysis of the multi-microbial consortium by Lactobacillus species against vaginal Dysbiosis among Ecuadorian women","volume":"12","author":"Pacha-Herrera","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3389\/fcimb.2020.00303","article-title":"Vaginal microbiota evaluation and lactobacilli quantification by qPCR in pregnant and non-pregnant women: a pilot study","volume":"10","author":"Pacha-Herrera","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref26","first-page":"321","article-title":"Vaginitis: diagnosis and treatment","volume":"97","author":"Paladine","year":"2018","journal-title":"Am. Fam. Physician"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2174\/1871526522666220501171551","article-title":"Native Iranian medicinal plants with anti-vaginal infection properties: a systematic review","volume":"22","author":"Rashidipour","year":"2022","journal-title":"Infect. Disord. Drug Targets"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1186\/s13104-022-06114-z","article-title":"Lactobacilli displacement and Candida albicans inhibition on initial adhesion assays: a probiotic analysis","volume":"15","author":"Rodr\u00edguez-Arias","year":"2022","journal-title":"BMC. Res. Notes"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"18358","DOI":"10.1038\/s41598-020-74655-z","article-title":"Vaginal microbiota evaluation and prevalence of key pathogens in ecuadorian women: an epidemiologic analysis","volume":"10","author":"Salinas","year":"2020","journal-title":"Sci. Rep."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1113\/JP271694","article-title":"The vaginal microbiota, host defence and reproductive physiology","volume":"595","author":"Smith","year":"2017","journal-title":"J. Physiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1177\/0956462420913435","article-title":"Aerobic vaginitis - an underdiagnosed cause of vaginal discharge - narrative review","volume":"31","author":"Sonthalia","year":"2020","journal-title":"Int. J. STD AIDS"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00404-020-05821-x","article-title":"Non-antibiotic treatment of bacterial vaginosis-a systematic review","volume":"303","author":"Tidbury","year":"2021","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e1002478","DOI":"10.1371\/journal.pmed.1002478","article-title":"The vaginal microbiome and sexually transmitted infections are interlinked: consequences for treatment and prevention","volume":"14","author":"van de Wijgert","year":"2017","journal-title":"PLoS Med."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/S1461-5347(00)00296-0","article-title":"The scope and potential of vaginal drug delivery","volume":"3","author":"Vermani","year":"2000","journal-title":"Pharm. Sci. Technol. Today"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3390\/cells12010092","article-title":"Repeated superovulation accelerates primordial follicle activation and atresia","volume":"12","author":"Wang","year":"2022","journal-title":"Cells"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"190","DOI":"10.4103\/japtr.JAPTR_3_19","article-title":"Antimicrobial activity of a novel polyherbal combination for the treatment of vaginal infection","volume":"10","author":"Yadav","year":"2019","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.3791\/3382-v","article-title":"Protocols for vaginal inoculation and sample collection in the experimental mouse model of Candida vaginitis","volume":"8","author":"Yano","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3389\/fmicb.2018.00198","article-title":"Streptococcus agalactiae inhibits Candida albicans hyphal development and diminishes host vaginal mucosal TH17 response","volume":"9","author":"Yu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"115806","DOI":"10.1016\/j.diagmicrobio.2022.115806","article-title":"Characteristics and potential diagnostic ability of vaginal microflora in patients with aerobic vaginitis using 16S ribosomal RNA sequencing","volume":"105","author":"Zeng","year":"2023","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"814883","DOI":"10.3389\/fphar.2022.814883","article-title":"Berberine inhibits the adhesion of Candida albicans to vaginal epithelial cells","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"4943","DOI":"10.1002\/ptr.7123","article-title":"Clinical research on traditional Chinese medicine treatment for bacterial vaginosis","volume":"35","author":"Zhao","year":"2021","journal-title":"Phytother. Res."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1341878\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T04:11:42Z","timestamp":1716783102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1341878\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,27]]},"references-count":41,"alternative-id":["10.3389\/fmicb.2024.1341878"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1341878","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,27]]},"article-number":"1341878"}}