Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.
The group B streptococcus (GBS) is the most important cause of life-threatening bacterial infections in newborn infants. Protective immunity to GBS infection is elicited by several surface proteins, one of which, the beta protein, is known to bind human IgA-Fc. Here, we show that the beta protein also binds human factor H (FH), a negative regulator of complement activation. Absorption experiments with whole human plasma demonstrated binding of FH to a GBS strain expressing beta protein but not to an isogenic beta-negative mutant. This binding was due to a direct interaction between beta and FH, as shown by experiments with purified proteins. Inhibition tests and studies with beta fragments demonstrated that FH and IgA-Fc bind to separate and nonoverlapping regions in beta. Heparin, a known ligand for FH, specifically inhibited the binding between beta and FH, suggesting that FH has overlapping binding sites for beta and heparin. Bacteria-bound FH retained its complement regulatory activity, implying that beta-expressing GBS may use bound FH to evade complement attack. The finding that beta protein binds FH adds to a growing list of interactions between human pathogens and complement regulatory proteins, supporting the notion that these interactions are of general importance in bacterial pathogenesis.
Areschoug
Thomas
T
Department of Medical Microbiology, Dermatology and Infection, Lund University, Sölvegatan 23, Lund SE-22362, Sweden. thomas.areschoug@mmb.lu.se
Stålhammar-Carlemalm
Margaretha
M
Karlsson
Ingrid
I
Lindahl
Gunnar
G
D015703:Antigens, CD / Q000097:blood / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017242:Complement Factor H / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D011961:Receptors, Fc / Q000097:blood / Q000378:metabolism*; D013291:Streptococcus / Q000378:metabolism*
D015703:Antigens, CD; D001426:Bacterial Proteins; C493495:CFH protein, human; D017931:DNA Primers; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D017242:Complement Factor H