title: In vivo binding of complement regulator factor H by Streptococcus pneumoniae.
abstract: Pneumococcal surface protein C (PspC) binds to the complement regulatory protein factor H (FH), which inhibits alternative pathway activation. In the present study, using a mouse model of systemic infection and flow-cytometric analyses, we demonstrated an in vivo interaction between FH and pneumococci and showed differential FH binding during bacteremia. Flow-cytometric analyses of pneumococci harvested after intraperitoneal (ip) challenge demonstrated increased binding of FH, compared with that after intravenous (iv) challenge. Real-time polymerase chain reaction analyses of PspC mRNA showed that, relative to pneumococci grown in vitro, those recovered from the blood of mice 24 h after iv challenge exhibited 23-fold higher mRNA levels; however, after ip challenge, PspC mRNA induction was increased 870-fold. A subsequent increase in PspC expression was detected by flow cytometry using a monoclonal antibody against PspC. Furthermore, pneumococci with FH bound to complement before exposure had increased proliferation, compared with pneumococci not pretreated with FH. These results suggest that the interaction between PspC and FH contributes to pneumococcal virulence.
authors.affiliation: Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216, USA.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Quin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Carmicle
authors.forename: Sandhya
authors.initials: S
authors.lastname: Dave
authors.forename: Michael K
authors.initials: MK
authors.lastname: Pangburn
authors.forename: Jason P
authors.initials: JP
authors.lastname: Evenhuis
authors.forename: Larry S
authors.initials: LS
authors.lastname: McDaniel
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D011008:Pneumococcal Infections / Q000382:microbiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000378:metabolism* / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D012333:RNA, Messenger; D017242:Complement Factor H