Multiple specificities of the staphylococcal and streptococcal fibronectin-binding microbial surface components recognizing adhesive matrix molecules

Danny Joh, Pietro Speziale, Sivashankarappa Gurusiddappa, Jeanette Manor, Magnus Höök

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Many pathogenic Gram-positive bacteria express fibronectin (Fn)-binding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), most of which have a similar structural organization with a primary ligand-binding domain consisting of 3-6 repeats of 40-50 amino-acid- residue motifs. The MSCRAMMs appear to preferentially bind to the N-terminal region of Fn, which is composed of five type-I modules. Here we report that the Fn-binding MSCRAMM FnbpA of Staphylococcus aureus contains a second ligand-binding domain located outside the repeat units. In addition, several sites in the Fn N-terminus presented as recombinant type-I module pairs bind to the repeat domain of the MSCRAMM. All of the MSCRAMMs analyzed, which include FnbpA of Staphylococcus aureus, Sfb of Streptococcus pyogenes, and FnbA and FnbB of Streptococcus dysgalactiae, were shown to bind to multiple sites in the N-terminal domain of Fn. By dissecting the repeat domain of FnbpA using synthetic peptides and recombinant fragments, we show that discrete, different motifs are responsible for the binding to individual sites in Fn, rather than a common motif being able to bind to several pairs of type-I Fn modules. The C-terminal half of many of the MSCRAMM repeat units contain a common motif, which is shown here to bind to the type-I module pair 4 and 5. In addition, some of the repeat units of FnbpA contain N-terminal motifs which bound to the type-I module pairs 1-2 and 2-3, respectively. These latter binding motifs appear to be partly overlapping and dependent on flanking sequences. Fluorescence polarization experiments using fluorescein- labeled MSCRAMM peptides and recombinant type-I Fn module pairs revealed dissociation constants of 1-13 μM. It was also shown that the fluorescein- labeled peptides differed in their primary binding sites on Fn.

Original languageEnglish (US)
Pages (from-to)897-905
Number of pages9
JournalEuropean Journal of Biochemistry
Volume258
Issue number2
DOIs
StatePublished - Dec 1 1998

Keywords

  • Bacterial adhesion
  • Fibronectin
  • Staphylococcus aureus
  • Streptococcus dysgalactiae
  • Streptococcus pyogenes

ASJC Scopus subject areas

  • Biochemistry

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