Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood
Bacterial infective endocarditis remains a disease with considerable morbidity and mortality. Of the numerous bacteria that can enter the bloodstream, certain oral commensal viridans group streptococci are among the major causative organisms of endocarditis. However, mechanisms underlying this selectivity are incompletely understood. Interactions between adhesins of such bacteria and human platelet sialoglycans are believed to play an important role in this selectivity, by facilitating bacterial adherence to damaged heart valves. Nevertheless, the molecular requirements for these interactions are not fully explored. Particularly, it is unclear whether selective targeting of platelets by these bacteria actually occurs in fluid human whole blood, an environment where numerous potential sialoglycan competitors exist. In the present work, we have addressed these important issues. We characterize in detail the glycan-binding spectra of a series of serine-rich repeat adhesins of oral streptococci. For the first time, we demonstrate that oral streptococci can indeed selectively target platelets in whole human blood. As a proof of concept, we also show that soluble recombinant bacterial adhesin binding region proteins can block the preferred platelet-bacterial interactions in whole blood. The knowledge gained from this study may help the development of novel preventive or therapeutic approaches against infective endocarditis.
Vyšlo v časopise:
Oral Streptococci Utilize a Siglec-Like Domain of Serine-Rich Repeat Adhesins to Preferentially Target Platelet Sialoglycans in Human Blood. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004540
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004540
Souhrn
Bacterial infective endocarditis remains a disease with considerable morbidity and mortality. Of the numerous bacteria that can enter the bloodstream, certain oral commensal viridans group streptococci are among the major causative organisms of endocarditis. However, mechanisms underlying this selectivity are incompletely understood. Interactions between adhesins of such bacteria and human platelet sialoglycans are believed to play an important role in this selectivity, by facilitating bacterial adherence to damaged heart valves. Nevertheless, the molecular requirements for these interactions are not fully explored. Particularly, it is unclear whether selective targeting of platelets by these bacteria actually occurs in fluid human whole blood, an environment where numerous potential sialoglycan competitors exist. In the present work, we have addressed these important issues. We characterize in detail the glycan-binding spectra of a series of serine-rich repeat adhesins of oral streptococci. For the first time, we demonstrate that oral streptococci can indeed selectively target platelets in whole human blood. As a proof of concept, we also show that soluble recombinant bacterial adhesin binding region proteins can block the preferred platelet-bacterial interactions in whole blood. The knowledge gained from this study may help the development of novel preventive or therapeutic approaches against infective endocarditis.
Zdroje
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