Staphylococcus aureus surface protein SdrE binds complement regulator factor H as an immune evasion tactic.
Similar to other highly successful invasive bacterial pathogens, Staphylococcus aureus recruits the complement regulatory protein factor H (fH) to its surface to inhibit the alternative pathway of complement. Here, we report the identification of the surface-associated protein SdrE as a fH-binding protein using purified fH overlay of S. aureus fractionated cell wall proteins and fH cross-linking to S. aureus followed by mass spectrometry. Studies using recombinant SdrE revealed that rSdrE bound significant fH whether from serum or as a purified form, in both a time- and dose-dependent manner. Furthermore, rSdrE-bound fH exhibited cofactor functionality for factor I (fI)-mediated cleavage of C3b to iC3b which correlated positively with increasing amounts of fH. Expression of SdrE on the surface of the surrogate bacterium Lactococcus lactis enhanced recruitment of fH which resulted in increased iC3b generation. Moreover, surface expression of SdrE led to a reduction in C3-fragment deposition, less C5a generation, and reduced killing by polymorphonuclear cells. Thus, we report the first identification of a S. aureus protein associated with the staphylococcal surface that binds factor H as an immune evasion mechanism.
Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia, United States of America. sharpja@evms.edu
Julia A
JA
Sharp
Charlene G
CG
Echague
Pamela S
PS
Hair
Michael D
MD
Ward
Julius O
JO
Nyalwidhe
Joan A
JA
Geoghegan
Timothy J
TJ
Foster
Kenji M
KM
Cunnion
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D003030:Coagulase / Q000737:chemistry / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D015936:Complement C5a / Q000096:biosynthesis; D017242:Complement Factor H / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology* / Q000378:metabolism*
D001426:Bacterial Proteins; C515944:ClfA protein, Staphylococcus aureus; D003030:Coagulase; D011994:Recombinant Proteins; C118507:SdrE protein, Staphylococcus aureus; D003179:Complement C3b; D015936:Complement C5a; D017242:Complement Factor H