{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:11:05Z","timestamp":1792681865578,"version":"4.5.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004740","name":"Fondazione del Monte di Bologna e Ravenna","doi-asserted-by":"publisher","award":["N\u00b0329bis\/2017"],"award-info":[{"award-number":["N\u00b0329bis\/2017"]}],"id":[{"id":"10.13039\/501100004740","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Gardnerella vaginalis<\/jats:italic>\n                    (GV) is an anaerobic bacterial species involved in the pathogenesis of bacterial vaginosis (BV), a condition of vaginal dysbiosis associated with adverse pregnancy outcomes. GV strains are categorized into four clades, characterized by a different ability to produce virulence factors, such as sialidase. We investigated the distribution of GV clades and sialidase genes in the vaginal ecosystem of a cohort of pregnant women, assessing the correlations between GV clades and the whole vaginal microbiome. A total of 61 Caucasian pregnant women were enrolled. Their vaginal swabs, collected both at the first and third trimester of pregnancy, were used for (i) evaluation of the vaginal status by Nugent score, (ii) vaginal microbiome profiling by 16S rRNA sequencing, (iii) detection and quantification of GV clades and sialidase A gene by qPCR assays. DNA of at least one GV clade was detected in most vaginal swabs, with clade 4 being the most common one. GV clade 2, together with the presence of multiple clades (&gt;2 simultaneously), were significantly associated with a BV condition. Significantly higher GV loads and sialidase gene levels were found in BV cases, compared to the healthy status. Clade 2 was related to the major shifts in the vaginal microbial composition, with a decrease in\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    and an increase in several BV-related taxa. As the number of GV clades detected simultaneously increased, a group of BV-associated bacteria tended to increase as well, while\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    tended to decrease. A negative correlation between sialidase gene levels and\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    , and a positive correlation with\n                    <jats:italic>Gardnerella<\/jats:italic>\n                    ,\n                    <jats:italic>Atopobium<\/jats:italic>\n                    ,\n                    <jats:italic>Prevotella<\/jats:italic>\n                    ,\n                    <jats:italic>Megasphaera<\/jats:italic>\n                    , and\n                    <jats:italic>Sneathia<\/jats:italic>\n                    were observed. Our results added knowledge about the interactions of GV clades with the inhabitants of the vaginal microbiome, possibly helping to predict the severity of BV and opening new perspectives for the prevention of pregnancy-related complications.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0269590","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:58:33Z","timestamp":1655215113000},"page":"e0269590","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Gardnerella vaginalis clades in pregnancy: New insights into the interactions with the vaginal microbiome"],"prefix":"10.1371","volume":"17","author":[{"given":"Marco","family":"Severgnini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Morselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Camboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Ceccarani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Salvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Zagonari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Patuelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Federica","family":"Pedna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Sambri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7253-8799","authenticated-orcid":true,"given":"Claudio","family":"Foschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-9557","authenticated-orcid":true,"given":"Clarissa","family":"Consolandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Marangoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"pone.0269590.ref001","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1113\/JP271694","article-title":"The vaginal microbiota, host defense and reproductive physiology","volume":"595","author":"SB Smith","year":"2017","journal-title":"J Physiol"},{"key":"pone.0269590.ref002","doi-asserted-by":"crossref","first-page":"14095","DOI":"10.1038\/s41598-019-50410-x","article-title":"Diversity of vaginal microbiome and metabolome during genital infections","volume":"9","author":"C Ceccarani","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0269590.ref003","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3389\/fmicb.2018.00600","article-title":"Insights Into Vaginal Bacterial Communities and Metabolic Profiles of Chlamydia trachomatis Infection: Positioning Between Eubiosis and Dysbiosis","volume":"9","author":"C Parolin","year":"2018","journal-title":"Front Microbiol"},{"key":"pone.0269590.ref004","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev.med.51.1.349","article-title":"Bacterial vaginosis","volume":"51","author":"JD Sobel","year":"2000","journal-title":"Annu Rev Med"},{"key":"pone.0269590.ref005","doi-asserted-by":"crossref","first-page":"e00204","DOI":"10.1128\/mBio.00204-15","article-title":"Metabolic signatures of bacterial vaginosis","volume":"6","author":"S Srinivasan","year":"2015","journal-title":"mBio"},{"key":"pone.0269590.ref006","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s40291-019-00382-5","article-title":"Quantitation of all Four Gardnerella vaginalis Clades Detects Abnormal Vaginal Microbiota Characteristic of Bacterial Vaginosis More Accurately than Putative G. vaginalis Sialidase A Gene Count","volume":"23","author":"E Shipitsyna","year":"2019","journal-title":"Mol Diagn Ther"},{"key":"pone.0269590.ref007","doi-asserted-by":"crossref","first-page":"813520","DOI":"10.3389\/fcimb.2021.813520","article-title":"Sialidase Activity in the Cervicovaginal Fluid Is Associated With Changes in Bacterial Components of Lactobacillus-Deprived Microbiota","volume":"11","author":"CST Ferreira","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"pone.0269590.ref008","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1128\/JB.01965-07","article-title":"Functional and phylogenetic characterization of Vaginolysin, the human-specific cytolysin from Gardnerella vaginalis","volume":"190","author":"SE Gelber","year":"2008","journal-title":"J Bacteriol"},{"key":"pone.0269590.ref009","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1097\/01.AOG.0000183594.45524.d2","article-title":"Adherent biofilms in bacterial vaginosis","volume":"106","author":"A Swidsinski","year":"2005","journal-title":"Obstet Gynecol"},{"key":"pone.0269590.ref010","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1128\/JB.00056-12","article-title":"Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars","volume":"194","author":"A Ahmed","year":"2012","journal-title":"J Bacteriol"},{"key":"pone.0269590.ref011","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12879-017-2501-y","article-title":"Prevalence and distribution of Gardnerella vaginalis subgroups in women with and without bacterial vaginosis","volume":"17","author":"M Janulaitiene","year":"2017","journal-title":"BMC Infect Dis"},{"key":"pone.0269590.ref012","first-page":"454","article-title":"Gardnerella vaginalis Clade Distribution Is Associated With Behavioral Practices and Nugent Score in Women Who Have Sex With Women","volume":"221","author":"EL Plummer","year":"2020","journal-title":"J Infect Dis"},{"key":"pone.0269590.ref013","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1007\/s10096-017-2933-8","article-title":"Gardnerella vaginalis population dynamics in bacterial vaginosis","volume":"36","author":"DW Hilbert","year":"2017","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"pone.0269590.ref014","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1099\/jmm.0.066407-0","article-title":"Identification, quantification and subtyping of Gardnerella vaginalis in noncultured clinical vaginal samples by quantitative PCR","volume":"63","author":"SV Balashov","year":"2014","journal-title":"J Med Microbiol"},{"key":"pone.0269590.ref015","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.fertnstert.2015.09.037","article-title":"Maternal microbiome and pregnancy outcomes","volume":"104","author":"C Fox","year":"2015","journal-title":"Fertil Steril"},{"key":"pone.0269590.ref016","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.anaerobe.2016.09.001","article-title":"The role of the bacterial microbiota on reproductive and pregnancy health","volume":"42","author":"DB Nelson","year":"2016","journal-title":"Anaerobe"},{"key":"pone.0269590.ref017","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s12884-016-1073-y","article-title":"Bacterial vaginosis and adverse outcomes among full-term infants: a cohort study","volume":"16","author":"AS Dingens","year":"2016","journal-title":"BMC Pregnancy Childbirth"},{"key":"pone.0269590.ref018","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1111\/j.1471-0528.2011.03020.x","article-title":"Aerobic vaginitis in pregnancy","volume":"118","author":"G Donders","year":"2011","journal-title":"BJOG"},{"key":"pone.0269590.ref019","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12905-019-0748-8","article-title":"Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes","volume":"19","author":"J Yano","year":"2019","journal-title":"BMC Womens Health"},{"key":"pone.0269590.ref020","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/JCM.00851-09","article-title":"Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis","volume":"48","author":"M Zozaya-Hinchliffe","year":"2010","journal-title":"J Clin Microbiol"},{"key":"pone.0269590.ref021","doi-asserted-by":"crossref","first-page":"e0120979","DOI":"10.1371\/journal.pone.0120979","article-title":"Evaluation of the Versant CT\/GC DNA 1.0 assay (kPCR) for the detection of extra-genital Chlamydia trachomatis and Neisseria gonorrhoeae infections","volume":"10","author":"A Marangoni","year":"2015","journal-title":"PLoS One"},{"key":"pone.0269590.ref022","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.3390\/pathogens10121546","article-title":"Distribution of ermB, ermF, tet(W), and tet(M) Resistance Genes in the Vaginal Ecosystem of Women during Pregnancy and Puerperium","volume":"10","author":"M Severgnini","year":"2021","journal-title":"Pathogens"},{"key":"pone.0269590.ref023","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1471-2105-13-31","article-title":"PANDAseq: paired-end assembler for illumina sequences","volume":"13","author":"AP Masella","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"pone.0269590.ref024","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"Correspondence QIIME allows analysis of high throughput community sequencing data Intensity normalization improves color calling in SOLiD sequencing","volume":"7","author":"JG Caporaso","year":"2010","journal-title":"Nat Methods"},{"key":"pone.0269590.ref025","first-page":"081257","article-title":"UNOISE2: Improved error-correction for Illumina 16S and ITS amplicon sequencing","author":"RC Edgar","year":"2016","journal-title":"BioRxiv"},{"key":"pone.0269590.ref026","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Q Wang","year":"2007","journal-title":"Appl Environ Microbiol"},{"key":"pone.0269590.ref027","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1038\/ismej.2010.133","article-title":"UniFrac: An effective distance metric for microbial community comparison","volume":"5","author":"C Lozupone","year":"2011","journal-title":"ISME J"},{"key":"pone.0269590.ref028","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.diagmicrobio.2015.10.006","article-title":"Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis","volume":"84","author":"JA Schuyler","year":"2016","journal-title":"Diagn Microbiol Infect Dis"},{"key":"pone.0269590.ref029","doi-asserted-by":"crossref","first-page":"450.e1","DOI":"10.1016\/j.ajog.2010.12.061","article-title":"Gardnerella vaginalis comprises three distinct genotypes of which only two produce sialidase","volume":"204","author":"GL Santiago","year":"2011","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0269590.ref030","unstructured":"Oksanen J, Blanchet FG, Kindt R, Legendre, Minchin PR, O\u2019Hara RB, et al. Package \u201cVegan\u201d. R Package Version 2.0\u201310. 2013. https:\/\/cran.r-project.org\/src\/contrib\/Archive\/vegan\/vegan_2.0-10.tar.gz (accessed on 22 February 2022)."},{"key":"pone.0269590.ref031","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/BF02289756","article-title":"Point biserial correlation coefficient and its generalization","volume":"25","author":"SD Gupta","year":"1960","journal-title":"Psychometrika"},{"key":"pone.0269590.ref032","doi-asserted-by":"crossref","first-page":"e0172522","DOI":"10.1371\/journal.pone.0172522","article-title":"The presence of the putative Gardnerella vaginalis sialidase A gene in vaginal specimens is associated with bacterial vaginosis biofilm","volume":"12","author":"L Hardy","year":"2017","journal-title":"PLoS One"},{"key":"pone.0269590.ref033","doi-asserted-by":"crossref","first-page":"e0171856","DOI":"10.1371\/journal.pone.0171856","article-title":"The influence of sexual activity on the vaginal microbiota and Gardnerella vaginalis clade diversity in young women","volume":"12","author":"LA Vodstrcil","year":"2017","journal-title":"PLoS One"},{"key":"pone.0269590.ref034","doi-asserted-by":"crossref","first-page":"e0146510","DOI":"10.1371\/journal.pone.0146510","article-title":"Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya","volume":"11","author":"JJ Schellenberg","year":"2016","journal-title":"PLoS One"},{"key":"pone.0269590.ref035","doi-asserted-by":"crossref","first-page":"e0200625","DOI":"10.1371\/journal.pone.0200625","article-title":"Phenotypic characterization of Gardnerella vaginalis subgroups suggests differences in their virulence potential","volume":"13","author":"M Janulaitiene","year":"2018","journal-title":"PLoS One"},{"key":"pone.0269590.ref036","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anaerobe.2017.05.012","article-title":"Quantification, Isolation and Characterization of Bifidobacterium From the Vaginal Microbiomes of Reproductive Aged Women","volume":"47","author":"AC Freitas","year":"2017","journal-title":"Anaerobe"},{"key":"pone.0269590.ref037","doi-asserted-by":"crossref","first-page":"779376","DOI":"10.3389\/fcimb.2021.779376","article-title":"A New PNA-FISH Probe Targeting Fannyhessea vaginae","volume":"11","author":"LGV Sousa","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"pone.0269590.ref038","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1086\/506621","article-title":"The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy","volume":"194","author":"CS Bradshaw","year":"2006","journal-title":"J Infect Dis"},{"key":"pone.0269590.ref039","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/OLQ.0000000000001204","article-title":"Characterization of the Vaginal Microbiome in Women of Reproductive Age From 5 Regions in Brazil","volume":"47","author":"C Marconi","year":"2020","journal-title":"Sex Transm Dis"},{"issue":"14","key":"pone.0269590.ref040","doi-asserted-by":"crossref","first-page":"5230","DOI":"10.1074\/jbc.RA118.006221","article-title":"Identification and characterization of NanH2 and NanH3, enzymes responsible for sialidase activity in the vaginal bacterium Gardnerella vaginalis","volume":"294","author":"LS Robinson","year":"2019","journal-title":"J Biol Chem"},{"key":"pone.0269590.ref041","doi-asserted-by":"crossref","first-page":"702370","DOI":"10.3389\/fmolb.2021.702370","article-title":"Pre-Pregnancy Diet and Vaginal Environment in Caucasian Pregnant Women: An Exploratory Study","volume":"8","author":"M Dall\u2019Asta","year":"2021","journal-title":"Front Mol Biosci"},{"key":"pone.0269590.ref042","doi-asserted-by":"crossref","first-page":"528202","DOI":"10.3389\/fimmu.2020.528202","article-title":"Recent Insights on the Maternal Microbiota: Impact on Pregnancy Outcomes","volume":"11","author":"N Di Simone","year":"2020","journal-title":"Front Immunol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269590","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T13:59:14Z","timestamp":1655215154000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0269590"}},"subtitle":[],"editor":[{"given":"Sylvia Maria","family":"Bruisten","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0269590","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]}}}