bacteriophage lysin mediates the binding of streptococcus mitis to human platelets through interaction with fibrinogen噬菌体细胞溶解酶介导的绑定链球菌对人类血小板通过与纤维蛋白原的交互.pdf

Bacteriophage Lysin Mediates the Binding of Streptococcus mitis to Human Platelets through Interaction with Fibrinogen 1 2 3 1 2 1 Ho Seong Seo , Yan Q. Xiong , Jennifer Mitchell , Ravin Seepersaud , Arnold S. Bayer , Paul M. Sullam * 1 Division of Infectious Diseases, Veterans Affairs Medical Center and the University of California, San Francisco, California, United States of America, 2 Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, United States of America, 3 University College, Dublin, Ireland Abstract The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contributes to platelet binding via its direct interaction with fibrinogen. Far Western blotting of platelets revealed that fibrinogen was the major membrane- associated protein bound by lysin. Analysis of lysin binding with purified fibrinogen in vitro confirmed that these proteins could bind directly, and that this interaction was both saturable and inhibitable. Lysin bound both the Aa and Bb chains of fibrinogen, but not the c subunit. Binding of lysin to the Bb chain was further localized to a region within the fibrinogen D fragment. Disruption of the SF100 lysin gene resulted in an 83 63.1% reduction (mean 6 SD) in binding to immobilized fibrinogen by this mutant strain (PS1006). Preincubation of this isogenic mutant with purified lysin restored fibrinogen binding to wild type levels. When tested in a co-inf