Bacteriophage Lysin Mediates the Binding of Streptococcus mitis to Human Platelets through Interaction with Fibrinogen

PLoS Pathogens

Yan Q. Xiong¹  Arnold S. Bayer¹  Ho Seong Seo²  Paul M. Sullam²  Ravin Seepersaud²  Jennifer Mitchell³ 

[1] Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, California, United States of America;Division of Infectious Diseases, Veterans Affairs Medical Center and the University of California, San Francisco, California, United States of America;University College, Dublin, Ireland

关键词: Fibrinogen;    Endocarditis;    Pneumococcus;    Cell walls;    Enzyme-linked immunoassays;    Platelets;    Bacterial pathogens;    Pathogenesis;   

DOI  :  10.1371/journal.ppat.1001047

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 Aα and Bβ chains of fibrinogen, but not the γ subunit. Binding of lysin to the Bβ chain was further localized to a region within the fibrinogen D fragment. Disruption of the SF100 lysin gene resulted in an 83±3.1% reduction (mean ± 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-infection model of endocarditis, loss of lysin expression resulted in a significant reduction in virulence, as measured by achievable bacterial densities (CFU/g) within vegetations, kidneys, and spleens. These results indicate that bacteriophage-encoded lysin is a multifunctional protein, representing a new class of fibrinogen-binding proteins. Lysin appears to be cell wall-associated through its interaction with choline. Once on the bacterial surface, lysin can bind fibrinogen directly, which appears to be an important interaction for the pathogenesis of endocarditis.

【 授权许可】

CC BY