title: New potential role of serum apolipoprotein E mediated by its binding to clumping factor A during Staphylococcus aureus invasive infections to humans.
abstract: Staphylococcus aureus is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes S. aureus binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient S. aureus bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the S. aureus virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the S. aureus surface may sequester ApoE and blunt its host defence function against S. aureus-invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents.
authors: Department of Pharmacy Practice, School of Pharmacy, Hampton University, Kittrell Hall, Hampton, VA 23668, USA.|Department of Pediatrics, Eastern Virginia Medical School, E.V. Williams Hall, 855 W. Brambleton Avenue, Norfolk, VA 23510, USA.|Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Organization of African Unity St., Abbassia, Cairo 11566, Egypt.
authors: Walid F
authors: WF
authors: Elkhatib
authors: Department of Pediatrics, Eastern Virginia Medical School, E.V. Williams Hall, 855 W. Brambleton Avenue, Norfolk, VA 23510, USA.
authors: Pamela S
authors: PS
authors: Hair
authors: Leroy T. Canoles Jr Cancer Research Center, Eastern Virginia Medical School, 651 Colley Avenue, Norfolk, VA, USA.|Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School 700 West Olney Road, Norfolk, VA, USA.
authors: Julius O
authors: JO
authors: Nyalwidhe
authors: Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, VA 23507, USA.|Children's Specialty Group, 601 Children's Lane, Norfolk, VA 23507, USA.|Department of Pediatrics, Eastern Virginia Medical School, E.V. Williams Hall, 855 W. Brambleton Avenue, Norfolk, VA 23510, USA.
authors: Kenji M
authors: KM
authors: Cunnion
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D001422:Bacterial Adhesion; D003030:Coagulase / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D013203:Staphylococcal Infections / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase