Adhesins, Bacterial, Bacterial Adhesion, Bacterial Outer Membrane Proteins, Biofilms, Carrier Proteins, Extracellular Matrix, Host-Pathogen Interactions, Humans, Membrane Proteins, Platelet Activation, Streptococcus gordonii, Virulence Factors
We gratefully acknowledge receipt of funding from The Wellcome Trust of a Clinical Training Fellowship #097285 for J.A.H.
A range of Streptococcus bacteria are able to interact with blood platelets to form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human oral cavity and amongst the common pathogens isolated from subjects with infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence protein A (PadA), in S. gordonii mediate adherence and activation of platelets. In this study, we demonstrate that PadA binds activated platelets and that an NGR (Asparagine-Glycine-Arginine) motif within a 657 amino acid residue N-terminal fragment of PadA is responsible for this, together with two other integrin-like recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate binding of S. gordonii to cellular fibronectin and vitronectin, and to promote formation of biofilms. Evidence is presented that PadA and Hsa are each reliant on the other's active presentation on the bacterial cell surface, suggesting cooperativity in functions impacting both colonization and pathogenesis.
Pharmacy and Pharmaceutical Sciences
Haworth JA, Jenkinson HF, Petersen HJ, Back CR, Brittan JL, Kerrigan SW, Nobbs AH. Concerted functions of Streptococcus gordonii surface proteins PadA and Hsa mediate activation of human platelets and interactions with extracellular matrix. Cellular Microbiology. 2017;19(1)
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