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

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

The Dynamics of the Regulation of Labor in Developing and Developed Countries since 1960

This paper examines both the determinants and the effects of changes in the rigidity of labor market legislation across countries over time. Recent research identifies the origin of the legal system as being a major determinant of the cross-country variation in the rigidity of employment protection legislation. However, the supporting evidence is largely confined to levels of regulation and is almost exclusively based on international cross-section data for the post-1995 period. This paper introduces a new index capturing the rigidity of employment protection legislation (LAMRIG) for an unbalanced panel of more than 140 countries over time starting in 1960. Although the importance of legal origins in explaining the level of rigidity of labor regulations across countries is replicated using LAMRIG, their explanatory power is much weakened for changes over time (1960-2004.) More important as determinants of such changes are the level of development and other reforms such as trade liberalization. With respect to the effects of changes in the rigidity of labor regulations on growth and inequality, which have been very controversial in the literature, results with LAMRIG support Freeman’s conjecture that changes in rigidity do not systematically affect economic growth but do lower income inequality.http://deepblue.lib.umich.edu/bitstream/2027.42/133054/1/wp1037.pd

Variations in binding of mammalian fibrinogens to streptococci groups A, B, C, E, G and to Staphylococcus aureus

Twenty-eight beta-hemolytic streptococci of groups A, B, E, G and Streptococcus equisimilis as well as four Staphylococcus aureus strains were tested for their ability to bind fibrinogen preparations from different animal species: homo, baboon, rabbit, rat, guinea-pig, dog, horse, pig, cow and sheep. The patterns of binding indicated differences in the structures of the bacterial fibrinogen receptors. There were higher binding levels in streptococci groups A, G, and S. equisimilis than in representative group B and E strains. Considerable differences in the binding capacity were found within streptococci groups A and E. Group C and group G strains showed rather similar patterns and could be further divided into high-level and low-level binding strains. There is no correlation between binding levels of different animal fibrinogen preparations and the strains isolated from corresponding animals. Recent studies by others have shown that resistance to phagocytosis is mediated by fibrinogen-binding in streptococci group A. The existence of similar fibrinogen-binding structures in several streptococcal species indicates an important role with a definite survival value. It also suggests that M or T protein analogues are present in streptococci groups C, G and E