{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:59:00Z","timestamp":1770271140553,"version":"3.49.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"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. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Group B streptococcus (GBS) harbors many virulence factors but there is limited data regarding their importance in colonization in pregnancy and early-onset disease (EOD) in the newborn. We hypothesized that colonization and EOD are associated with different distribution and expression of virulence factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 36 GBS EOD and 234 GBS isolates collected during routine screening. Virulence genes (pilus-like structures-<jats:italic>PI-1, PI-2a, PI-2b<\/jats:italic>; <jats:italic>rib<\/jats:italic> and <jats:italic>hvgA<\/jats:italic>) presence and expression were identified by PCR and qRT-PCR. Whole genome sequencing (WGS) and comparative genomic analyses were used to compare coding sequences (CDSs) of colonizing and EOD isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serotype III (ST17) was significantly associated with EOD and serotype VI (ST1) with colonization. <jats:italic>hvgA<\/jats:italic> and <jats:italic>rib<\/jats:italic> genes were more prevalent among EOD isolates (58.3 and 77.8%, respectively; <jats:italic>p<\/jats:italic> &amp;lt; 0.01). The pilus loci <jats:italic>PI-2b<\/jats:italic> and <jats:italic>PI-2a<\/jats:italic> were more prevalent among EOD isolates (61.1%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01), while the pilus loci <jats:italic>PI-2a<\/jats:italic> and <jats:italic>PI-1<\/jats:italic> among colonizing isolates (89.7 and 93.1% vs. 55.6 and 69.4%, <jats:italic>p<\/jats:italic> &amp;lt; 0.01). qRT PCR analysis revealed that <jats:italic>hvgA<\/jats:italic> was barely expressed in colonizing isolates, even though the gene was detected. Expression of the <jats:italic>rib<\/jats:italic> gene and <jats:italic>PI-2b<\/jats:italic> was two-fold higher in EOD isolates compared to colonizing isolates. Transcription of <jats:italic>PI-2a<\/jats:italic> was three-fold higher in colonizing isolates compared to EOD isolates. ST17 isolates (associated with EOD) had a smaller genome size compared ST1 and the genome was more conserved relative to the reference strain and ST17 isolates. In a multivariate logistic regression analysis virulence factors independently associated with EOD were serotype 3, and <jats:italic>PI-1<\/jats:italic> and <jats:italic>PI-2a<\/jats:italic> was protective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>There was a significant difference in the distribution of <jats:italic>hvg A<\/jats:italic>, <jats:italic>rib<\/jats:italic>, and <jats:italic>PI<\/jats:italic> genes among EOD (serotype III\/ST17) and colonizing (serotype VI\/ST1) isolates suggesting an association between invasive disease and these virulence factors. Further study is needed to understand the contribution of these genes to GBS virulence.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1093288","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T07:07:26Z","timestamp":1676272046000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Group B streptococcus virulence factors associated with different clinical syndromes: Asymptomatic carriage in pregnant women and early-onset disease in the newborn"],"prefix":"10.3389","volume":"14","author":[{"given":"Yulia","family":"Schindler","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galia","family":"Rahav","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Israel","family":"Nissan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orit","family":"Treygerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Prajgrod","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bracha Zukerman","family":"Attia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronit","family":"Raz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gal Zizelski","family":"Valenci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Tekes-Manova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmin","family":"Maor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1007\/s10096-015-2487-6","article-title":"Molecular epidemiology and distribution of serotypes, genotypes, and antibiotic resistance genes of Streptococcus agalactiae clinical isolates from Guelma, Algeria and Marseille, France.","volume":"34","author":"Bergal","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241517298","article-title":"Mutation frequency and biological cost of antibiotic resistance in Helicobacter pylori.","volume":"98","author":"Bj\u00f6rkholm","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-020-05603-5","article-title":"Prevalence, serotypes and virulence genes of Streptococcus agalactiae isolated from pregnant women with 35\u201337weeks of gestation.","volume":"21","author":"Bobadilla","year":"2021","journal-title":"BMC Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/srep38523","article-title":"Real-time PCR-based serotyping of Streptococcus agalactiae.","volume":"6","author":"Breeding","year":"2016","journal-title":"Sci. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/j.micinf.2005.11.010","article-title":"Genomic diversity and evolution within the species Streptococcus agalactiae.","volume":"8","author":"Brochet","year":"2006","journal-title":"Microbes Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1017\/S0950268811000616","article-title":"Molecular characterization of capsular polysaccharides and surface protein genes in relation to genetic similarity of group B streptococci isolated from Polish pregnant women.","volume":"140","author":"Brzychczy-W\u0142och","year":"2012","journal-title":"Epidemiol. Infect."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01265","article-title":"Genomic analysis reveals multi-drug resistance clusters in group B Streptococcus CC17 hypervirulent isolates causing neonatal invasive disease in southern mainland China.","volume":"7","author":"Campisi","year":"2016","journal-title":"Front. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.2147\/IDR.S203454","article-title":"A vaccine against group B Streptococcus: Recent advances.","volume":"13","author":"Carreras-Abad","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B9","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gki008","article-title":"VFDB: A reference database for bacterial virulence factors.","volume":"33","author":"Chen","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.pedn.2004.05.012","article-title":"A history of neonatal group B Streptococcus with its related morbidity and mortality rates in the United States.","volume":"19","author":"Dermer","year":"2004","journal-title":"J. Pediatr. Nurs."},{"key":"B11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nrmicro.2015.13","article-title":"Within-host evolution of bacterial pathogens.","volume":"14","author":"Didelot","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1111\/j.1365-2958.2006.05190.x","article-title":"Assembly and role of pili in group B streptococci.","volume":"60","author":"Dramsi","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s10096-014-2265-x","article-title":"Antimicrobial susceptibility profiles, serotype distribution and virulence determinants among invasive, non-invasive and colonizing Streptococcus agalactiae (Group B Streptococcus) from Malaysian patients.","volume":"34","author":"Eskandarian","year":"2015","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01230-20","article-title":"American Society for Microbiology provides 2020 guidelines for detection and identification of group B Streptococcus.","volume":"59","author":"Filkins","year":"2021","journal-title":"J. Clin. Microbiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4489","DOI":"10.1016\/j.vaccine.2021.06.046","article-title":"Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women.","volume":"39","author":"Fischer","year":"2021","journal-title":"Vaccine"},{"key":"B16","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1073\/pnas.1012579108","article-title":"Birth and death of genes linked to chromosomal inversion.","volume":"108","author":"Furuta","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B17","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1093\/molbev\/msaa278","article-title":"Common adaptive strategies underlie within-host evolution of bacterial pathogens.","volume":"38","author":"Gatt","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.1007\/s10096-020-03992-8","article-title":"Streptococcus agalactiae in pregnant women: Serotype and antimicrobial susceptibility patterns over five years in Eastern Sicily (Italy).","volume":"39","author":"Genovese","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.1128\/JCM.00999-07","article-title":"Molecular epidemiology and distribution of serotypes, surface proteins, and antibiotic resistance among group B streptococci in Italy.","volume":"45","author":"Gherardi","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0010043","article-title":"Gain and loss of multiple genes during the evolution of Helicobacter pylori.","volume":"1","author":"Gressmann","year":"2005","journal-title":"PLoS Genet."},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.1016\/j.mib.2022.102197","article-title":"Within-host evolution of bacterial pathogens during persistent infection of humans.","volume":"70","author":"Grote","year":"2022","journal-title":"Curr. Opin. Microbiol."},{"key":"B22","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.cmi.2015.05.039","article-title":"Group B Streptococcus neonatal invasive infections, France 2007-2012.","volume":"21","author":"Joubrel","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"B23","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ijregi.2022.07.002","article-title":"Molecular characterization and antimicrobial resistance of Streptococcus agalactiae isolated from pregnant women in Japan, 2017-2021.","volume":"4","author":"Kawaguchiya","year":"2022","journal-title":"IJID Reg."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1086\/314666","article-title":"Serotypes VI and VIII predominate among group B streptococci isolated from pregnant Japanese women.","volume":"179","author":"Lachenauer","year":"1999","journal-title":"J. Infect. Dis."},{"key":"B25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1126\/science.1111563","article-title":"Genome analysis reveals pili in group B Streptococcus.","volume":"309","author":"Lauer","year":"2005","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1097\/INF.0000000000002943","article-title":"Prevalence of capsular serotype, Pilus Island distribution, and antibiotic resistance in pediatric and adult invasive group B Streptococcus isolates: Data from a nationwide prospective surveillance study in Germany.","volume":"40","author":"Lohrmann","year":"2020","journal-title":"Pediatr. Infect. Dis. J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.tim.2007.10.010","article-title":"Pili in Gram-positive bacteria: Assembly, involvement in colonization and biofilm development.","volume":"16","author":"Mandlik","year":"2008","journal-title":"Trends Microbiol."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-6-116","article-title":"The frequency of genes encoding three putative group B streptococcal virulence factors among invasive and colonizing isolates.","volume":"6","author":"Manning","year":"2006","journal-title":"BMC Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1038\/ng1470","article-title":"Comparison of genome degradation in Paratyphi A and Typhi, human-restricted serovars of Salmonella enterica that cause typhoid.","volume":"36","author":"McClelland","year":"2004","journal-title":"Nat. Genet."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa151","article-title":"Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive group B Streptococci within the US: 2015\u20132017.","volume":"72","author":"McGee","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1111\/j.1469-0691.2011.03576.x","article-title":"Neonatal group B streptococcal disease: From pathogenesis to preventive strategies.","volume":"17","author":"Melin","year":"2011","journal-title":"Clin. Microbiol. Infect."},{"key":"B32","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/s0092-8674(02)00665-7","article-title":"Microbial minimalism: Genome reduction in bacterial pathogens.","volume":"108","author":"Moran","year":"2002","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-021-02186-2","article-title":"Prevalence, population structure, distribution of serotypes, pilus islands and resistance genes among erythromycin-resistant colonizing and invasive Streptococcus agalactiae isolates recovered from pregnant and non-pregnant women in Isfahan, Iran.","volume":"21","author":"Motallebirad","year":"2021","journal-title":"BMC Microbiol."},{"key":"B34","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1093\/molbev\/msaa323","article-title":"Genome reduction is associated with bacterial pathogenicity across different scales of temporal and ecological divergence.","volume":"38","author":"Murray","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0997-x","article-title":"Mash: Fast genome and metagenome distance estimation using MinHash.","volume":"17","author":"Ondov","year":"2016","journal-title":"Genome Biol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/jof4040128","article-title":"Recent advances in the use of Galleria mellonella model to study immune responses against human pathogens.","volume":"4","author":"Pereira","year":"2018","journal-title":"J. Fungi"},{"key":"B37","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1086\/591182","article-title":"Pilus backbone contributes to group B Streptococcus paracellular translocation through epithelial cells.","volume":"198","author":"Pezzicoli","year":"2008","journal-title":"J. Infect. Dis."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00602","article-title":"Streptococcus agalactiae non-pilus, cell wall-anchored proteins: Involvement in colonization and pathogenesis and potential as vaccine candidates.","volume":"9","author":"Pietrocola","year":"2018","journal-title":"Front. Immunol."},{"key":"B39","doi-asserted-by":"crossref","first-page":"615","DOI":"10.17843\/rpmesp.2021.384.8726","article-title":"[Molecular characterization of virulence (lmb, bca and rib) and macrolid resistance genes (ermB, ermTR and mefA) in clinical isolates of Streptococcus agalactiae].","volume":"38","author":"Pulido-Colina","year":"2021","journal-title":"Rev. Peru Med. Exp. Salud Publica"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009216","article-title":"Specific involvement of pilus type 2a in biofilm formation in group B Streptococcus.","volume":"5","author":"Rinaudo","year":"2010","journal-title":"PLoS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.1365-2958.2006.05225.x","article-title":"Identification of novel genomic islands coding for antigenic pilus-like structures in Streptococcus agalactiae.","volume":"61","author":"Rosini","year":"2006","journal-title":"Mol. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"S100","DOI":"10.1093\/cid\/cix658","article-title":"Maternal colonization with group B Streptococcus and serotype distribution worldwide: Systematic review and meta-analyses.","volume":"65","author":"Russell","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244450","article-title":"Group B Streptococcus serotypes associated with different clinical syndromes: Asymptomatic carriage in pregnant women, intrauterine fetal death, and early onset disease in the newborn.","volume":"15","author":"Schindler","year":"2020","journal-title":"PLoS One"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00437","article-title":"Group B streptococcal colonization, molecular characteristics, and epidemiology.","volume":"9","author":"Shabayek","year":"2018","journal-title":"Front. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1017\/S0950268806007515","article-title":"Distribution of novel and previously investigated virulence genes in colonizing and invasive isolates of Streptococcus agalactiae.","volume":"135","author":"Smith","year":"2007","journal-title":"Epidemiol. Infect."},{"key":"B46","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.vetmic.2019.06.008","article-title":"The distribution of clones of Streptococcus agalactiae (group B streptococci) among herdspersons and dairy cows demonstrates lack of host specificity for some lineages.","volume":"235","author":"S\u00f8rensen","year":"2019","journal-title":"Vet. Microbiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1093\/infdis\/jiw589","article-title":"Effect of the Streptococcus agalactiae virulence regulator CovR on the pathogenesis of urinary tract infection.","volume":"215","author":"Sullivan","year":"2017","journal-title":"J. Infect. Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1084\/jem.20092594","article-title":"The surface protein HvgA mediates group B Streptococcus hypervirulence and meningeal tropism in neonates.","volume":"207","author":"Tazi","year":"2010","journal-title":"J. Exp. Med."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1128\/JCM.03554-13","article-title":"Characterization of invasive group B Streptococcus strains from the greater Toronto area, Canada.","volume":"52","author":"Teatero","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"12391","DOI":"10.1073\/pnas.182380799","article-title":"Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae.","volume":"99","author":"Tettelin","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1093288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T07:07:35Z","timestamp":1676272055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1093288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":50,"alternative-id":["10.3389\/fmicb.2023.1093288"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1093288","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]},"article-number":"1093288"}}