Strain-level Genomic Analysis of Serotype, Genotype and Virulence Gene Composition of Group B Streptococcus

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2024 Nov 21

PMID 39569407

Authors

Zhen Zeng

Meng Li

Simin Zhu

Ke Zhang

Yifan Wu

Minzi Zheng

Yang Cao

Zhenyu Huang

Qinping Liao

Lei Zhang

Affiliations

Soon will be listed here.

Abstract

Introduction: GBS (group B streptococcus) is an opportunistic pathogen that can colonize healthy individuals but presents significant challenges in clinical obstetrics and gynecology, as it can cause miscarriage, preterm birth, and invasive infections in newborns. To develop specific and personalized preventative strategies, a better understanding of the epidemiological characteristics and pathogenic features of GBS is essential.

Methods: We conducted a comprehensive strain-level genomic analysis of GBS, examining serotype and genotype distributions, as well as the composition and correlations of virulence genes using the blastn-short mode of the BLAST program(v2.10.0+), mlstsoftware (https://github.com/tseemann/mlst), Snippy (v4.6.0), FastTree (v2.1.11) and iTOL. The coding sequence region of virulence factors was annotated by Prodigal (v2.6.3) and Glimmer(v3.02b). We further identified host protein interacting with Srr2 by mass spectrometry analysis.

Results: While certain genotypes showed strong serotype consistency, there was no significant association between overall serotypes and genotypes. However, the composition of virulence genes was more closely related to the phylogeny of GBS, among which simultaneous presence of Srr2 and HygA exhibit significant association with hypervirulence. Tubulin emerged as the most distinct and abundant hit. The specific interaction of Tubulin with Srr2-BR, rather than Srr1-BR, was further confirmed by immunoblotting.

Discussion: Considering the impact of cytoskeleton rearrangement on GBS pathogenesis, this observation offers a plausible explanation for the hypervirulence triggered by Srr2. Collectively, our findings indicate that in the future clinical practice, virulence gene detection should be given more attention to achieve precise GBS surveillance and disease prevention.

References

Jackson L, Hilsdon R, Farley M, Harrison L, Reingold A, Plikaytis B . Risk factors for group B streptococcal disease in adults. Ann Intern Med. 1995; 123(6):415-20. DOI: 10.7326/0003-4819-123-6-199509150-00003. View

Kong F, Gowan S, Martin D, James G, Gilbert G . Molecular profiles of group B streptococcal surface protein antigen genes: relationship to molecular serotypes. J Clin Microbiol. 2002; 40(2):620-6. PMC: 153396. DOI: 10.1128/JCM.40.2.620-626.2002. View

Gabrielsen C, Maeland J, Lyng R, Radtke A, Afset J . Molecular characteristics of Streptococcus agalactiae strains deficient in alpha-like protein encoding genes. J Med Microbiol. 2016; 66(1):26-33. DOI: 10.1099/jmm.0.000412. View

Alhhazmi A, Hurteau D, Tyrrell G . Epidemiology of Invasive Group B Streptococcal Disease in Alberta, Canada, from 2003 to 2013. J Clin Microbiol. 2016; 54(7):1774-1781. PMC: 4922093. DOI: 10.1128/JCM.00355-16. View

Baron M, Bolduc G, Goldberg M, Auperin T, Madoff L . Alpha C protein of group B Streptococcus binds host cell surface glycosaminoglycan and enters cells by an actin-dependent mechanism. J Biol Chem. 2004; 279(23):24714-23. DOI: 10.1074/jbc.M402164200. View

Verani J, McGee L, Schrag S . Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010; 59(RR-10):1-36. View

Manni M, Berkeley M, Seppey M, Zdobnov E . BUSCO: Assessing Genomic Data Quality and Beyond. Curr Protoc. 2021; 1(12):e323. DOI: 10.1002/cpz1.323. View

Guiney D, Lesnick M . Targeting of the actin cytoskeleton during infection by Salmonella strains. Clin Immunol. 2005; 114(3):248-55. DOI: 10.1016/j.clim.2004.07.014. View

Chang Y, Olson J, Louie A, Crocker P, Varki A, Nizet V . Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus. J Mol Med (Berl). 2014; 92(9):951-9. PMC: 4133643. DOI: 10.1007/s00109-014-1157-y. View

10.

Pietrocola G, Schubert A, Visai L, Torti M, Fitzgerald J, Foster T . FbsA, a fibrinogen-binding protein from Streptococcus agalactiae, mediates platelet aggregation. Blood. 2004; 105(3):1052-9. DOI: 10.1182/blood-2004-06-2149. View

11.

Breeding K, Ragipani B, Lee K, Malik M, Randis T, Ratner A . Real-time PCR-based serotyping of Streptococcus agalactiae. Sci Rep. 2016; 6:38523. PMC: 5133537. DOI: 10.1038/srep38523. View

12.

Pezzicoli A, Ruggiero P, Amerighi F, Telford J, Soriani M . Exogenous sialic acid transport contributes to group B streptococcus infection of mucosal surfaces. J Infect Dis. 2012; 206(6):924-31. DOI: 10.1093/infdis/jis451. View

13.

Gutekunst H, Eikmanns B, Reinscheid D . The novel fibrinogen-binding protein FbsB promotes Streptococcus agalactiae invasion into epithelial cells. Infect Immun. 2004; 72(6):3495-504. PMC: 415667. DOI: 10.1128/IAI.72.6.3495-3504.2004. View

14.

Rosa-Fraile M, Dramsi S, Spellerberg B . Group B streptococcal haemolysin and pigment, a tale of twins. FEMS Microbiol Rev. 2014; 38(5):932-46. PMC: 4315905. DOI: 10.1111/1574-6976.12071. View

15.

Allen U, Nimrod C, Macdonald N, Toye B, Stephens D, Marchessault V . Relationship between antenatal group B streptococcal vaginal colonization and premature labour. Paediatr Child Health. 2010; 4(7):465-9. PMC: 2827758. DOI: 10.1093/pch/4.7.465. View

16.

Delcher A, Bratke K, Powers E, Salzberg S . Identifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics. 2007; 23(6):673-9. PMC: 2387122. DOI: 10.1093/bioinformatics/btm009. View

17.

Benito-Jardon M, Strohmeyer N, Ortega-Sanchis S, Bharadwaj M, Moser M, Muller D . αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation. J Cell Biol. 2020; 219(12). PMC: 7644020. DOI: 10.1083/jcb.202004198. View

18.

Shabayek S, Spellerberg B . Group B Streptococcal Colonization, Molecular Characteristics, and Epidemiology. Front Microbiol. 2018; 9:437. PMC: 5861770. DOI: 10.3389/fmicb.2018.00437. View

19.

Jolley K, Maiden M . BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics. 2010; 11:595. PMC: 3004885. DOI: 10.1186/1471-2105-11-595. View

20.

Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A . Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. 2002; 51(RR-11):1-22. View