Streptococcal beta protein has separate binding sites for human factor H and IgA-Fc.

Research output: Contribution to journalArticle

Abstract

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 non-overlapping 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.

Details

Authors
  • Thomas Areschoug
  • Margaretha Stålhammar-Carlemalm
  • Ingrid Karlsson
  • Gunnar Lindahl
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area

Keywords

  • Binding Sites, Streptococcus/*metabolism, Non-U.S. Gov't, Support, Fc/blood/*metabolism, Antigens, CD/blood/*metabolism, Base Sequence, Bacterial Proteins/*metabolism, Receptors, Human, Complement Factor H/*metabolism, DNA Primers
Original languageEnglish
Pages (from-to)12642-12648
JournalJournal of Biological Chemistry
Volume277
Issue number15
Publication statusPublished - 2002
Publication categoryResearch
Peer-reviewedYes