title: Complement regulator C4BP binds to Staphylococcus aureus surface proteins SdrE and Bbp inhibiting bacterial opsonization and killing.
abstract: Staphylococcus aureus is a premier human pathogen and the most common cause of osteoarticular, wound, and implanted device infections. We recently demonstrated S. aureus efficiently binds the classical complement regulator C4b-binding protein (C4BP) inhibiting antibody-initiated complement-mediated opsonization. Here we identify S. aureus surface protein SdrE as a C4BP-binding protein. Recombinant SdrE and recombinant bone sialoprotein-binding protein (Bbp), an allelic variant of SdrE, both efficiently bound to C4BP in heat-inactivated human serum. We previously described SdrE as binding alternative pathway regulator factor H. Recombinant SdrE and Bbp efficiently bound C4BP and factor H in serum without apparent interference. Gain of function studies utilizing Lactococcus lactis clones expressing SdrE or Bbp increased serum C4BP and factor H binding, compared with empty-vector control (WT) approximately 2-fold. Correspondingly, classical pathway-mediated C3-fragment opsonization and bacterial killing by human neutrophils decreased by half for L. lactis clones expressing SdrE or Bbp compared with WT. In summary, we identify SdrE and allelic variant Bbp as S. aureus surface proteins that bind the complement regulator C4BP inhibiting classical pathway-mediated bacterial opsonization and killing.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, 855 West Brambleton Avenue, P.O. Box 1980, Norfolk, VA 23501-1980, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Hair
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, 855 West Brambleton Avenue, P.O. Box 1980, Norfolk, VA 23501-1980, USA.
authors.forename: Caitlin K
authors.initials: CK
authors.lastname: Foley
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA, USA.
authors.forename: Neel K
authors.initials: NK
authors.lastname: Krishna
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA, USA ; Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, 651 Colley Avenue, Norfolk, VA, USA.
authors.forename: Julius O
authors.initials: JO
authors.lastname: Nyalwidhe
authors.affiliation: Department of Microbiology, Trinity College, The University of Dublin, Dublin, Ireland.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.affiliation: Department of Microbiology, Trinity College, The University of Dublin, Dublin, Ireland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, 855 West Brambleton Avenue, P.O. Box 1980, Norfolk, VA 23501-1980, USA ; Children's Specialty Group, 601 Children's Lane, Norfolk, VA, USA ; The Children's Hospital of The King's Daughters, 601 Children's Lane, Norfolk, VA, USA.
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
keywords: C4BP; Complement; Opsonophagocytosis; SdrE; Staphylococcus aureus