Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

 Can Group B Streptococcus (GBS) strain diversity in carriage be recovered from low-abundance metagenomic samples? A simulation study (#256)

Ruchita Balasubramanian 1 , Lea Cavalli 1 , William P Hanage 1
  1. Harvard University, Boston, MA, United States

Group B Streptococcus (GBS) is a gut commensal and cause of neonatal invasive disease, potentially following vaginal dysbiosis(1). While maternal colonization is linked to neonatal disease, understanding GBS colonization dynamics across body sites remains critical. One hypothesis suggests vaginal colonization is seeded from the gut, given its gastrointestinal carriage(2). Without whole genome sequences from either niche, metagenomic samples offer an alternative to explore GBS strain diversity. However, low GBS abundance in the gut complicates strain typing.

We conducted a simulation study to assess GBS strain typing at low abundance. Using Seq2mgs, we created 78 synthetic metagenomes by spiking GBS reads into a background metagenome (Accession: SRR12344432) at relative abundances of 0.01X, 0.005X, 0.001X(3). For each clonal complex (CC), we used 2-3 publicly available GBS genomes to generate synthetic metagenomes. Using k-mer based tool StrainGE, we tested these synthetic metagenomes against 130 RefSeq reference genomes(4).

The GBS CC’s were accurately identified for all synthetic metagenomes except CC12 and CC452. CC12 samples were identified as a mix of ST7 and ST283, while 3/9 CC452 samples were identified as a mix of ST23 and ST452. ST mismatches are likely based on limitations of ST typing (based only on 7 housekeeping genes), and the particular heterogeneity of CC12(5,6).

Ultimately, our simulation shows the ability to accurately recapitulate GBS strain types despite low abundance in complex microbial backgrounds. This confirms the potential of using this approach on empirical metagenomic samples to investigate GBS dynamics across carriage niches

  1. 1. Le TM, Choi Y, Nguyen HDT, et al. Relationship between maternal Group B Streptococcal colonization and gestational vaginal microbiome composition: A pilot study. Indian Journal of Medical Microbiology 2023; 46: 100426.
  2. 2. van Kassel MN, Janssen SWCM, Kofman S, Brouwer MC, van de Beek D, Bijlsma MW. Prevalence of group B streptococcal colonization in the healthy non-pregnant population: a systematic review and meta-analysis. Clinical Microbiology and Infection 2021; 27: 968–80.
  3. 3. Van Camp P-J, Porollo A. SEQ2MGS: an effective tool for generating realistic artificial metagenomes from the existing sequencing data. NAR Genomics and Bioinformatics 2022; 4: lqac050.
  4. 4. StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities | Genome Biology | Full Text. https://genomebiology.biomedcentral.com/articles/10.1186/s13059-022-02630-0#Sec12 (accessed Jan 24, 2025).
  5. 5. Jones N, Bohnsack JF, Takahashi S, et al. Multilocus sequence typing system for group B streptococcus. J Clin Microbiol 2003; 41: 2530–6.
  6. 6. Hsu J-F, Chen Y-N, Chu S-M, et al. Clonal Complex 12 Serotype Ib Streptococcus agalactiae Strain Causing Complicated Sepsis in Neonates: Clinical Features and Genetic Characteristics. Microbiol Spectr; 11: e03778-22.