Selection, recombination, and virulence gene diversity among group B streptococcal genotypes

Abstract

Transmission of group B Streptococcus (GBS) from mothers to neonates during childbirth is a leading cause of neonatal sepsis and meningitis. Although subtyping tools have identified specific GBS phylogenetic lineages that are important in neonatal disease, little is known about the genetic diversity of these lineages or the roles that recombination and selection play in the generation of emergent genotypes. Here, we examined genetic variation, selection, and recombination in seven multilocus sequence typing (MLST) loci from 94 invasive, colonizing, and bovine strains representing 38 GBS sequence types and performed DNA sequencing and PCR-based restriction fragment length polymorphism analysis of several putative virulence genes to identify gene content differences between genotypes. Despite the low level of diversity in the MLST loci, a neighbor net analysis revealed a variable range of genetic exchange among the seven clonal complexes (CCs) identified, suggesting that recombination is partly responsible for the diversity observed between genotypes. Recombination is also important for several virulence genes, as some gene alleles had evidence for lateral gene exchange across divergent genotypes. The CC-17 lineage, which is associated with neonatal disease, is relatively homogeneous and therefore appears to have diverged independently with an exclusive set of virulence characteristics. These data suggest that different GBS genetic backgrounds have distinct virulence gene profiles that may be important for disease pathogenesis. Such profiles could be used as markers for the rapid detection of strains with an increased propensity to cause neonatal disease and may be considered useful vaccine targets.

FIG. 1.

Phylogenetic relationships of 38 GBS STs. The numbers at the different nodes represent bootstrap values, and only those relationships with >80% bootstrap support are indicated. The colored circles show the different CCs that contained STs grouping together with >87% bootstrap support. p distance, untransformed distance. Bovine strains are represented in CC-61 and by STs 67, 72, and 356.

FIG. 2.

Neighbor net analysis revealed a complex network with extensive recombination (shown as parallelograms) between 38 GBS STs. The circles highlight the CCs identified in the neighbor-joining phylogeny. p distance, untransformed distance.

FIG. 3.

Frequencies and distribution of major alleles representing five GBS virulence genes by CC ranked in order according to the neighbor-joining phylogenetic tree (Fig. 1). The frequencies of alleles specific to alpha C protein genes (A), cspA (B), gbs2018 (C), scpB (D), and sip (E) are indicated by different colors. Only STs that were part of a CC were plotted, as singleton STs located near each CC typically shared the same allele profile and thus should not be grouped together as one category.