title: Regulation and function of pilus island 1 in group B streptococcus.
abstract: Group B streptococcus (GBS) pili may enhance colonization and infection by mediating bacterial adhesion to host cells, invasion across endothelial and epithelial barriers, and resistance to bacterial ingestion and killing by host phagocytes. However, it remains unclear how pilus expression is regulated and how modulation of pilus production affects GBS interactions with the human host. We investigated the regulation and function of pilus island 1 (PI-1) pili in GBS strain 2603. We found that PI-1 gene expression was controlled by the CsrRS two-component system, by Ape1, an AraC-type regulator encoded by a divergently transcribed gene immediately upstream of PI-1, and by environmental pH. The response regulator CsrR repressed expression of Ape1, which is an activator of PI-1 gene expression. In addition, CsrR repressed PI-1 gene expression directly, independent of its regulation of Ape1. In vitro assays demonstrated specific binding of both CsrR and Ape1 to chromosomal DNA sequences upstream of PI-1. Pilus gene expression was activated by acidic pH, and this effect was independent of CsrRS and Ape1. Unexpectedly, characterization of PI-1 deletion mutants revealed that PI-1 pili do not mediate adhesion of strain 2603 to A549 respiratory epithelial cells, ME180 cervical cells, or VK2 vaginal cells in vitro. PI-1 pili reduced internalization and intracellular killing of GBS by human monocyte-derived macrophages, by approximately 50%, but did not influence complement-mediated opsonophagocytic killing by human neutrophils. These findings shed new light on the complex nature of pilus regulation and function in modulating GBS interactions with the human host.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Boston, Boston, Massachusetts, USA.
authors.forename: Shengmei
authors.initials: S
authors.lastname: Jiang
authors.forename: Su Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Puja
authors.initials: P
authors.lastname: Yadav
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Paoletti
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wessels
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000382:microbiology; D016296:Mutagenesis; D009154:Mutation; D013292:Streptococcus agalactiae / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins