1887

Abstract

is a crucial human pathogen expressing various immune-evasion proteins that interact with the host-cell molecules. Clumping factor A (ClfA) is a microbial surface protein that promotes binding to fibrinogen, and is associated with septic arthritis and infective endocarditis. In order to identify the major human serum proteins that bind the ClfA, we utilized recombinant ClfA region A in a plate-based assay. SDS-PAGE analysis of the bound proteins yielded five prominent bands, which were analysed by MS yielding apolipoprotein E (ApoE) as the predominant protein. ClfA-sufficient bound purified ApoE by more than one log greater than an isogenic ClfA-deficient mutant. An immunodot-blot assay yielded a linearity model for ClfA binding to human ApoE with a stoichiometric-binding ratio of 1.702 at maximal Pearson's correlation coefficient (0.927). These data suggest that ApoE could be a major and novel binding target for the virulence factor ClfA. Thus, ClfA recruitment of serum ApoE to the surface may sequester ApoE and blunt its host defence function against -invasive infections to humans. In this context, compounds that can block or suppress ClfA binding to ApoE might be utilized as prophylactic or therapeutic agents.

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2015-04-01
2019-12-13
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