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

Autor: Bensing BA; Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California, United States of America., Li L; Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, United States of America., Yakovenko O; Department of Bioengineering, University of Washington, Seattle, Washington, United States of America., Wong M; Department of Chemistry, University of California, Davis, California, United States of America., Barnard KN; Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America., Iverson TM; Departments of Pharmacology and Biochemistry, Vanderbilt University, Nashville, Tennessee, United States of America., Lebrilla CB; Department of Chemistry, University of California, Davis, California, United States of America., Parrish CR; Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America., Thomas WE; Department of Bioengineering, University of Washington, Seattle, Washington, United States of America., Xiong Y; Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California, United States of America.; David Geffen School of Medicine at UCLA, Los Angeles, California, United States of America., Sullam PM; Department of Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2019 Jun 24; Vol. 15 (6), pp. e1007896. Date of Electronic Publication: 2019 Jun 24 (Print Publication: 2019).
DOI: 10.1371/journal.ppat.1007896
Abstrakt: 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 GPIbα (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 GPIbα has a more heterogenous composition of modified sialic acids. The combined results suggest that streptococcal interaction with a minor O-glycan on GPIbα may be more important than the over-all affinity for GPIbα for pathogenic effects.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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