Multiple sites on Streptococcus gordonii surface protein PadA bind to platelet GPlIbIlla

作者：Keane Clara; Petersen Helen J; Tilley Dorothea O; Haworth Jennifer; Cox Dermot; Jenkinson Howard F; Kerrigan Steve W^*

来源：Thrombosis and Haemostasis, 2013, 110(6): 1278-1287.

DOI：10.1160/TH13-07-0580

• Bacterial surface protein
• platelet adhesion
• aggregation
• spreading
• dense granule release
• shear adhesion

Infective endocarditis is a life threatening disease caused by a bacterial infection of the endocardial surfaces of the heart. The oral pathogen, Streptococcus gordbnii is amongst the most common pathogens isolated from infective endocarditis patients. Previously we identified a novel cell wall protein expressed On S. gordonii called pia: telet adherence protein A (PadA) that specifically interacts with pia; telet GPIlb/111a. The interaction between PadA and GPIlb/Illa resulted; in firm platelet adhesion, dense granule secretion and platelet spreading on immobilised S. gordonii. This study set Out to identify specific ! motifs on the PadA protein that interacts with platelet GPIlb/111a. Pro; teomic analysis of the PadA protein identified two short amino acid motifs which have been previously Shown to be important for fibrinogen binding to GPIlb/Illa and contributing to the generation of out-side-in signalling. Site directed mutagenesis on the PadA protein in which (454)AGD was substituted to AAA, and the (383)RGT was substituted to AAA suggests the RGT motif has no role in supporting platelet adhesion however plays a role in dense granule secretion and platelet spreading. In contrast to this the AGD motif has no role to play in supporting firm platelet adhesion or dense granule secretion however plays a role in platelet spreading. These results suggest that multiple sites on S. gordonii PadA interact with GPIlb/Illa to mediate a number of platelet responses that likely contribute to the thrombotic complications of infective endocarditis.

• 出版日期2013-12