{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:10:24Z","timestamp":1790230224592,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011563","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty Research Development Fund, University of Auckland"},{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/W013630\/1"],"award-info":[{"award-number":["BB\/W013630\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Trichomonas vaginalis<\/jats:italic> is a human protozoan parasite that causes trichomoniasis, a prevalent sexually transmitted infection. Trichomoniasis is accompanied by a shift to a dysbiotic vaginal microbiome that is depleted of lactobacilli. Studies on co-cultures have shown that vaginal bacteria in eubiosis (e.g. <jats:italic>Lactobacillus gasseri<\/jats:italic>) have antagonistic effects on <jats:italic>T<\/jats:italic>. <jats:italic>vaginalis<\/jats:italic> pathogenesis, suggesting that the parasite might benefit from shaping the microbiome to dysbiosis (e.g. <jats:italic>Gardnerella vaginalis<\/jats:italic> among other anaerobes). We have recently shown that <jats:italic>T<\/jats:italic>. <jats:italic>vaginalis<\/jats:italic> has acquired NlpC\/P60 genes from bacteria, expanding them to a repertoire of nine TvNlpC genes in two distinct clans, and that TvNlpCs of clan A are active against bacterial peptidoglycan. Here, we expand this characterization to TvNlpCs of clan B. In this study, we show that the clan organisation of NlpC\/P60 genes is a feature of other species of <jats:italic>Trichomonas<\/jats:italic>, and that <jats:italic>Histomonas meleagridis<\/jats:italic> has sequences related to one clan. We characterized the 3D structure of TvNlpC_B3 alone and with the inhibitor E64 bound, probing the active site of these enzymes for the first time. Lastly, we demonstrated that TvNlpC_B3 and TvNlpC_B5 have complementary activities with the previously described TvNlpCs of clan A and that exogenous expression of these enzymes empower this mucosal parasite to take over populations of vaginal lactobacilli in mixed cultures. TvNlpC_B3 helps control populations of <jats:italic>L<\/jats:italic>. <jats:italic>gasseri<\/jats:italic>, but not of <jats:italic>G<\/jats:italic>. <jats:italic>vaginalis<\/jats:italic>, which action is partially inhibited by E64. This study is one of the first to show how enzymes produced by a mucosal protozoan parasite may contribute to a shift on the status of a microbiome, helping explain the link between trichomoniasis and vaginal dysbiosis. Further understanding of this process might have significant implications for treatments in the future.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011563","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T17:49:03Z","timestamp":1692208143000},"page":"e1011563","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["NlpC\/P60 peptidoglycan hydrolases of Trichomonas vaginalis have complementary activities that empower the protozoan to control host-protective lactobacilli"],"prefix":"10.1371","volume":"19","author":[{"given":"Michael J.","family":"Barnett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jully","family":"Pinheiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy R.","family":"Keown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Biboy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana-Wilhelmina","family":"Lucinescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waldemar","family":"Vollmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Hirt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2461-1917","authenticated-orcid":true,"given":"Augusto","family":"Simoes-Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Goldstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"ppat.1011563.ref001","unstructured":"The World Health Organization. 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