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Host\u2013bacteria and bacteria\u2013bacteria interactions are thought to contribute to the condition, but many of these functions have yet to be elucidated. Using untargeted metaproteomics, we identified 1068 host and 1418 bacterial proteins in a set of cervicovaginal lavage samples collected from 20 participants with BV and 9 who were negative for the condition. We identified Dialister micraerophilus as a major producer of malodorous polyamines and identified a syntrophic interaction between this organism and Fannyhessea vaginae that leads to increased production of putrescine, a metabolite characteristic of BV. Although formate synthesis has not previously been noted in BV, we discovered diverse bacteria associated with the condition express pyruvate formate-lyase enzymes in vivo and confirm these organisms secrete formic acid in vitro. Sodium hypophosphite efficiently inhibited this function in multiple taxa. We also found that the fastidious organism Coriobacteriales bacterium DNF00809 can metabolize formic acid secreted by Gardnerella vaginalis, representing another syntrophic interaction. We noted an increased abundance of the host epithelial repair protein transglutaminase 3 in the metaproteomic data, which we confirmed by enzyme-linked immunosorbent assay. Other proteins identified in our samples implicate Finegoldia magna and Parvimonas micra in the production of malodorous trimethylamine. Some bacterial proteins identified represent novel targets for future therapeutics to disrupt BV communities and promote vaginal colonization by commensal lactobacilli.<\/jats:p>","DOI":"10.1093\/ismejo\/wraf055","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:53:11Z","timestamp":1750924391000},"source":"Crossref","is-referenced-by-count":11,"title":["Syntrophic bacterial and host\u2013microbe interactions in bacterial vaginosis"],"prefix":"10.1093","volume":"19","author":[{"given":"Elliot M","family":"Lee","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel O","family":"Purvine","sequence":"additional","affiliation":[{"name":"Environmental Molecular Sciences Division, Pacific Northwest National Laboratory, 3335 Innovation Blvd , Richland, WA 99354 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina L","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen P","family":"Leiser","sequence":"additional","affiliation":[{"name":"Chemical and Biological Signatures, Pacific Northwest National Laboratory , 1100 Dexter Avenue N, Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean C","family":"Proll","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S","family":"Minot","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijel","family":"Djukovic","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, University of Washington , 1959 NE Pacific Street, Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Raftery","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine, University of Washington , 1959 NE Pacific Street, Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Johnston","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]},{"name":"Department of Medicine, University of Washington , 1959 NE Pacific Street, Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N","family":"Fredricks","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center , 1100 Fairview Ave N Seattle, WA 98109 ,","place":["United States"]},{"name":"Department of Medicine, University of Washington , 1959 NE Pacific Street, Seattle, WA 98195 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke L","family":"Deatherage Kaiser","sequence":"additional","affiliation":[{"name":"Chemical and Biological Signatures, Pacific Northwest National Laboratory , 1100 Dexter Avenue N, Seattle, WA 98109 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"2025063015061957800_ref1","doi-asserted-by":"publisher","first-page":"e37818","DOI":"10.1371\/journal.pone.0037818","article-title":"Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria","volume":"7","author":"Srinivasan","year":"2012","journal-title":"PLoS One"},{"key":"2025063015061957800_ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12866-019-1388-8","article-title":"Vaginal pH measured in vivo: lactobacilli determine pH and lactic acid concentration","volume":"19","author":"O\u2019Hanlon","year":"2019","journal-title":"BMC 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