Evidence for Rare Capsular Switching in Streptococcus agalactiae

Abstract

The polysaccharide capsule is a major antigenic factor in Streptococcus agalactiae (Lancefield group B streptococcus [GBS]). Previous observations suggest that exchange of capsular loci is likely to occur rather frequently in GBS, even though GBS is not known to be naturally transformable. We sought to identify and characterize putative capsular switching events, by means of a combination of phenotypic and genotypic methods, including pulsed-field gel electrophoretic profiling, multilocus sequence typing, and surface protein and pilus gene profiling. We show that capsular switching by horizontal gene transfer is not as frequent as previously suggested. Serotyping errors may be the main reason behind the overestimation of capsule switching, since phenotypic techniques are prone to errors of interpretation. The identified putative capsular transformants involved the acquisition of the entire capsular locus and were not restricted to the serotypespecific central genes, the previously suggested main mechanism underlying capsular switching. Our data, while questioning the frequency of capsular switching, provide clear evidence for in vivo capsular transformation in S. agalactiae, which may be of critical importance in planning future vaccination strategies against this pathogen. Streptococcus agalactiae (group B streptococcus [GBS]) is primarily a colonizing agent of the genitourinary and gastrointestinal tracts, but it is also a leading cause of bacterial sepsis and meningitis in neonates and is increasingly associated with invasive infections in adults (39). The capsular polysaccharide is a major GBS virulence factor and also the main target of antibody-mediated killing (11). In the last decade, conjugated multivalent vaccines have been developed and proved to be highly immunogenic, raising the possibility of the prevention of perinatal GBS disease through maternal immunization (38).Nine capsular types are recognized: Ia, Ib and II to VIII, along with a new provisional serotype IX, recently proposed (19). Comparison of the capsular locus genes suggested that the structural diversity of the capsular polysaccharide is associated with the genetic diversity of the capsular locus, possibly driven by horizontal gene transfer (9, 24). Capsular serotyping has been the classical method used in epidemiological studies to differentiate GBS isolates, although further characterization of GBS diversity includes the use of a broad range of DNAbased typing methods, such as restriction fragment length polymorphisms (RFLP), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Both PFGE and MLST have provided new clues about the population structure of S. agalactiae, particularly the recognition of diverse lineages among serotype III that were shown to differ in virulence potential and tropism (16,25,26,31,41). Although the distinction of lineages within a particular serotype has proved useful, a complete correlation between capsular type and the lineages defined by MLST was not found (4,21,22). Moreover, w...

Distribution of pilus islands of group B streptococcus associated with maternal colonization and invasive disease in South Africa

“…Our data were consistent with previous studies from industrialized countries in that all isolates were associated with the presence of either PI-2a or PI-2b. PI-1 and PI-2b were almost always present together, and the presence of PI-1 in PI-2a harbouring isolates was largely dependent on serotype, with the majority of serotype Ib, II and V isolates harbouring these two pilus islands together, whereas the majority of type Ia isolates were associated PI-2a on its own (Margarit et al, 2009;Martins et al, 2010). This is, to the best of our knowledge, the first study from a developing country wherein a substantial population of colonization and invasive disease isolates has been analysed, allowing better comparisons between strains from invasive disease and maternal colonization.…”

“…This is, to the best of our knowledge, the first study describing the prevalence of pilus islands in isolates from vaginally colonized mothers, and infants with invasive disease, collected outside of Europe and the USA (Margarit et al, 2009;Martins et al, 2010). There are currently no published data on the pilus island distribution from subSaharan Africa where GBS remains the most frequently isolated pathogens in neonates (Berkley et al, 2005;Gray et al, 2007;Madhi et al, 2003;Milledge et al, 2005).…”

Serotype distribution and resistance genes associated with macrolide and fluoroquinolone resistance in Streptococcus agalactiae isolates from a hospital in southern Taiwan

“…[28,29] Further investigation is required to determine whether serotype switching is involved in the observed differences in ermB-associated serotypes. [30] The prevalence of CLI and ERY resistance in the tested isolates differed, [25,27] and ermB was present in 91.9% of ERY-resistant isolates and in 84.0% of CLI-resistant isolates in Korea. [25] However, in this study, ermB was present in those isolates with a higher population resistant to AZM (90.6%), ERY (95.9%), or CLI (94.1%).…”

On the origin of Group B Streptococcus from disease outbreaks in wild marine fish in Australia

“…Capsular specificity genes are present in the accessory genomes, and can be exchanged within the same species or between species by lateral genetic transfer in order to quickly adapt to new environment (Martins et al, 2010;Medini et al, 2005). The polysaccharide capsule is made up by the arrangements of four sugar components into a unique repeated unit (Brochet et al, 2006).…”

“…The capsular polysaccharides (CPSs) are the major virulence factors in GBS Martins et al, 2010;Millard et al, 2012) and are present in most encapsulated Gram-positive bacteria.…”