In human strains of all other lineages, however, many (27%) lacked PI-1 altogether suggesting that it is more important for colonization and disease progression in certain genetic backgrounds. As we have observed the same degree of diversity in many other GBS surface proteins [25, 26], it is possible that individual strains utilize different adherence mechanisms to colonize the host. Further stratification by the type of PI-2 variant demonstrated

that 98% of neonatal CC-17 strains had PI-1 with PI-2b; none of the strains with this PI profile from other lineages originated from neonates, suggesting that PI-2b may be important for neonatal disease. Interestingly, all 53 cpsIII CC-17 strains contained san1519 allele 2 encoding the PI-2b BP, the major component of the pilus structure JNK inhibitor [24], also suggesting a specific role for this allele in neonatal disease. Although the diversity of san1519 is low, the allelic distribution varied among human and bovine strains with the latter exclusively carrying allele 3. Outside of CC-17, PI-1/2b-positive strains of CC-1 had san1519 allele 1 and represented rare cps types

(e.g., IV, VII, and VIII). The extensive genetic diversity seen across CCs reflects the independent divergence of these strain populations and highlights features that may influence host specificity and pathogenic potential. Additional studies are needed, however, to examine whether strains of different lineages and PI profiles have an enhanced ability to colonize and/or invade human learn more epithelial cells. It would also be worthwhile to compare PI distributions among strains associated with uncomplicated infections such as urinary tract infections and wound infections since a prior study identified different STs to be associated with these types of infections [30]. Unlike san1519, the PI-2a BP gene, gbs59, was diverse in strains of lineages previously associated with maternal colonization (e.g., CC-1 and CC-23).

Presumably, diversity within PI-2a enhances versatility and enhances the ability to colonize multiple hosts and niches. Support for this hypothesis comes from the reportedly high frequencies of CCs 1 and 23 in asymptomatic women [5] as well as their isolation from bovines [7, 8, 31] and other animal species Liothyronine Sodium [32, 33]. As antigenic variation is important for evasion of host immune responses, the high level of diversity in gbs59 may be the result of strong selective pressures encountered within different hosts. The presence of identical alleles among unrelated strains (Figure 4) also suggests that gbs59 is a “hot spot” for recombination, while low sequence variability in san1519 of PI-2b is evidence of a more constrained evolutionary history. Because there is a clear correlation between phylogenetic lineage and PI profile, both vertical inheritance and horizontal gene transfer have likely contributed to the PI distribution observed.