Journal Article

Comparative genomic analysis of hypervirulent group B streptococcus of ST12/serotype Ib suggests potential virulence factors

Zhou, Kaixin, Sun, Zhewei, Sun, Jingyong, Guan, Ming, Xu, Xiaogang

2025

Overview

Background Group B streptococcus is a leading cause of neonatal invasive diseases. ST12/serotype Ib GBS isolate, the second most prevalent lineage in East Asia, has aroused increasing attention, as a growing body of reports suggests they may be more virulent and fatal than the ST17/serotype III strain. Results Sag37, an ST12/serotype Ib isolate, was recovered from a fatal neonatal case and exhibited features suggestive of hypervirulence. To define this lineage’s prevalence and virulence, we analyzed 432 non-duplicate GBS isolates collected in Shanghai (2016 ~ 2022), and subtyped them by multilocus sequence typing (MLST) and capsular serotyping via a multiplex polymerase chain reaction. MLST revealed 50 sequence types, with ST10 and ST19 being most common. Nine clonal complexes were identified using the eBURST program, dominated by CC12 and CC19. Among seven serotypes identified, Ib was most prevalent, followed by III, V and Ia. Guided by the epidemiological data, additional clinical ST12/serotype Ib isolates, along with representative strains from other STs/serotypes, were selected for virulence assessment. For survival, 8-week-old CD1 mice were challenged subcutaneously with 1 × 10 8 CFU and monitored for 7 days. ST12/serotype Ib isolates caused 100% mortality within 48 h, whereas other GBS subtypes resulted in delayed or no mortality. For the median lethal dose (LD 50 ), mice received intraperitoneal doses from 10 3 to 10 8 CFU; logistic regression estimated LD 50 values ranging from ≤ 10 3 to ≥ 10 8 CFU within ST12/serotype Ib, indicating marked intra-lineage heterogeneity. To further investigate the molecular mechanisms underlying the hypervirulence, whole-genome sequencing was conducted on 33 ST12/serotype Ib GBS strains identified herein. A pyseer-based genome-wide association study was performed using LD 50 as a quantitative trait. Multiple genetic variations potentially related to virulence were identified, providing insights into the molecular basis of hypervirulence of ST12/serotype Ib GBS. Conclusions This study underscored the correlation between ST12/serotype Ib GBS isolates and hypervirulence, and further and revealed multiple candidate loci potentially associated with this phenotype. These findings highlighted the need for ongoing surveillance and functional investigation of emerging GBS lineages. Clinical trial number Not applicable.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Animals / Bacteria / Biological Microscopy / Biomedical and Life Sciences / Care and treatment / Childbirth & labor / China - epidemiology / Complications and side effects / Disease / Diseases / Epidemiology / Female / Gene sequencing / Genes / Genetic diversity / Genetic testing / Genome, Bacterial / Genome-wide association studies / Genomes / Genomic analysis / Genomics / Group B streptococcus / Heterogeneity / Humans / Hypervirulence / Infant, Newborn / Infants (Newborn) / Laboratory animals / Lethal dose / Life Sciences / Mice / Microbiology / Molecular modelling / Mortality / Multilocus Sequence Typing / Mycology / Neonates / Nosocomial infections / Parasitology / Pathogenesis / Phenotypes / Phylogenetics / Phylogeny / Polymerase chain reaction / Regression analysis / Sepsis / Serogroup / Serotypes / Serotyping / Software / ST12/serotype Ib / Streptococcal infections / Streptococcal Infections - microbiology / Streptococcus agalactiae - classification / Streptococcus agalactiae - genetics / Streptococcus agalactiae - isolation & purification / Streptococcus agalactiae - pathogenicity / Streptococcus infections / Vagina / Virology / Virulence / Virulence (Microbiology) / Virulence - genetics / Virulence factors / Virulence Factors - genetics / Whole genome sequencing / Womens health