Sequence diversity in the A domain of Staphylococcus aureus fibronectin-binding protein A.
Citation:
Loughman, A, Sweeney, T, Keane, FM, Pietrocola, G, Speziale, P, Foster, TJ, Sequence diversity in the A domain of Staphylococcus aureus fibronectin-binding protein A., BMC Microbiology, 8, 8, 2008, 74Download Item:
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Abstract:
Background: Fibronectin-binding protein A (FnBPA) mediates adhesion of Staphylococcus aureus
to fibronectin, fibrinogen and elastin. We previously reported that S. aureus strain P1 encodes an
FnBPA protein where the fibrinogen/elastin-binding domain (A domain) is substantially divergent in
amino acid sequence from the archetypal FnBPA of S. aureus NCTC8325, and that these variations
created differences in antigenicity. In this study strains from multilocus sequence types (MLST) that
spanned the genetic diversity of S.aureus were examined to determine the extent of FnBPA A
domain variation within the S. aureus population and its effect on ligand binding and immunocrossreactivity.
Results: Seven different isotype forms (I ? VII) of the FnBPA A domain were identified which were
between 66 to 76% identical in amino acid sequence in any pair-wise alignment. The fnbA allelic
variants in strains of different multilocus sequence type were identified by DNA hybridization using
probes specific for sequences encoding the highly divergent N3 sub-domain of different isotypes.
Several isotypes were not restricted to specific clones or clonal complexes but were more widely
distributed. It is highly likely that certain fnbA genes have been transferred horizontally. Residues
lining the putative ligand-binding trench were conserved, which is consistent with the ability of each
A domain isotype to bind immobilized fibrinogen and elastin by the dock-latch-lock mechanism.
Variant amino acid residues were mapped on a three-dimensional model of the FnBPA A domain
and were predicted to be surface-exposed. Polyclonal antibodies raised against the recombinant
isotype I A domain bound that protein with a 4 ? 7 fold higher apparent affinity compared to the
A domains of isotypes II ? VII, while some monoclonal antibodies generated against the isotype I A
domain showed reduced or no binding to the other isotypes.
Conclusion: The FnBPA A domain occurs in at least 7 different isotypes which differ antigenically
and exhibit limited immuno-crossreactivity, yet retain their ligand-binding functions. Antigenic
variation of the FnBPA A domain may aid S. aureus to evade the host's immune responses. These
findings have implications for the development of vaccines or immunotherapeutics that target
FnBPA.
Sponsor
Grant Number
Health Research Board (HRB)
Author's Homepage:
http://people.tcd.ie/tfosterDescription:
PUBLISHED
Author: FOSTER, TIMOTHY; SWEENEY, TARA
Type of material:
Journal ArticleCollections:
Series/Report no:
BMC Microbiology8
8
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Full text availableKeywords:
MicrobiologyDOI:
http://dx.doi.org/10.1186/1471-2180-8-74Licences: