title: Dual roles of PspC, a surface protein of Streptococcus pneumoniae, in binding human secretory IgA and factor H.
abstract: Streptococcus pneumoniae, also known as the pneumococcus, contains several surface proteins that along with the polysaccharide capsule function in antiphagocytic activities and evasion of the host immune system. These pneumococcal proteins interact with the host immune system in various ways and possess a wide range of biological activities that suggests that they may be involved at different stages of pneumococcal infection. PspC, also known as CbpA and SpsA, is one of several pneumococcal surface proteins that binds host proteins, including factor H (FH) and secretory IgA (sIgA) via the secretory component. Previous work by our laboratory has demonstrated that PspC on the surface of live pneumococcal cells binds FH. This paper provides evidence that FH activity is maintained in the presence of PspC and that the PspC binding site is located in the short consensus repeat 6-10 region of FH. We also report for the first time that although both FH and sIgA binding has been localized to the alpha-helical domain of PspC, the binding of FH to PspC is not inhibited by sIgA. ELISA, surface plasmon resonance, and flow cytometry indicate that the two host proteins do not compete for binding with PspC and likely do not share the same binding sites. We confirmed by Western analysis that the binding sites are separate using recombinant PspC proteins. These PspC variants bind FH yet fail to bind sIgA. Thus, we conclude that FH and sIgA can bind concurrently to the alpha-helical region of PspC.
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Dave
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carmicle
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Michael K
authors.initials: MK
authors.lastname: Pangburn
authors.forename: Larry S
authors.initials: LS
authors.lastname: McDaniel
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D001665:Binding Sites; D015153:Blotting, Western; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D001426:Bacterial Proteins; C493495:CFH protein, human; D007071:Immunoglobulin A, Secretory; C110344:SpsA protein, Streptococcus pneumoniae; D017242:Complement Factor H