Recognition of specific sialoglycan structures by oral streptococci impacts the severity of endocardial infection

Abstract

Streptococcus gordonii and Streptococcus sanguinis are primary colonizers of the tooth surface. Although generally non-pathogenic in the oral environment, they are a frequent cause of infective endocarditis. Both streptococcal species express a serine-rich repeat surface adhesin that mediates attachment to sialylated glycans on mucin-like glycoproteins, but the specific sialoglycan structures recognized can vary from strain to strain. Previous studies have shown that sialoglycan binding is clearly important for aortic valve infections caused by some S. gordonii, but this process did not contribute to the virulence of a strain of S. sanguinis. However, these streptococci can bind to different subsets of sialoglycan structures. Here we generated isogenic strains of S. gordonii that differ only in the type and range of sialoglycan structures to which they adhere and examined whether this rendered them more or less virulent in a rat model of endocarditis. The findings indicate that the recognition of specific sialoglycans can either enhance or diminish pathogenicity. Binding to sialyllactosamine reduces the initial colonization of mechanically-damaged aortic valves, whereas binding to the closely-related trisaccharide sialyl T-antigen promotes higher bacterial densities in valve tissue 72 hours later. A surprising finding was that the initial attachment of streptococci to aortic valves was inversely proportional to the affinity of each strain for platelets, suggesting that binding to platelets circulating in the blood may divert bacteria away from the endocardial surface. Importantly, we found that human and rat platelet GPIb alpha (the major receptor for S. gordonii and S. sanguinis on platelets) display similar O-glycan structures, comprised mainly of a di-sialylated core 2 hexasaccharide, although the rat GPIb alpha has a more heterogenous composition of modified sialic acids. The combined results suggest that streptococcal interaction with a minor O-glycan on GPIb alpha may be more important than the over-all affinity for GPIb alpha for pathogenic effects.

Author summary Infective endocarditis (IE) is a life-threatening infection of heart valves, and streptococci that normally reside in the mouth are a leading cause of this disease. Some oral streptococcal species express a protein on their surface that enables attachment to glycan (sugar) modifications on saliva proteins, an interaction that may be important for colonization of the tooth and other oral surfaces. These "Siglec-like adhesins" are hypervariable in the type and number of glycan structures they bind, ranging from just one to more than six of the structures displayed on the saliva proteins. If streptococci enter into the bloodstream, the Siglec-like adhesin can mediate attachment to similar glycans that decorate platelet or plasma proteins, which can impact the overall virulence of the organism. This study highlights how recognition of a specific type of glycan structure can cause a generally beneficial or neutral microbe to create damage to specific tissues-in this case the heart valves, illustrating one means by which commensal bacteria can become opportunistic or accidental pathogens. The findings further indicate that certain glycan-binding streptococci among the oral microbiota may be predisposed to produce infective endocarditis.