Despite ongoing surveillance and control efforts, group B Streptococcus (GBS) remains an important cause of infectious morbidity and mortality among newborns, as well as an increasing cause of invasive disease in adults. GBS vaccine development is a high priority, and a candidate conjugate polysaccharide vaccine is currently in human trials. This vaccine targets six of the ten known GBS serotypes, based on epidemiologic studies of invasive disease as well as rectovaginal carriage. Serotype distribution data are largely based on assays of single colonies from clinical samples. Based on our preliminary data, we hypothesize that carriage of non- vaccine type (NVT) GBS (serotypes VI-IX) is substantially more common than previously realized. Additionally, invasive infections due to NVT GBS are increasing in frequency. It is not known whether the less common GBS serotypes are intrinsically less fit than the more common ones with respect to colonization efficiency or pathogenicity. Likewise, the importance of recently characterized naturally occurring "capsule switch" GBS strains, in which the genetic locus that determines capsular type has transferred from one strain to another, remains incompletely understood. Here we propose a program of research designed to test hypotheses regarding the prevalence of (and risk factors for) colonization and invasive infection due to NVT GBS serotypes in human samples and to use newly developed techniques for GBS genome manipulation to understand the role of specific capsule and non-capsule factors in colonization fitness and pathogenesis in vivo.