Open AccessA novel sialic acid-binding adhesin present in multiple species contributes to the pathogenesis of Infective endocarditis
Author(s) -
Meztlli O. Gaytán,
Anirudh Singh,
Shireen A. Woodiga,
Surina Patel,
Seon-Sook An,
Arturo VeraPonce de León,
Sean McGrath,
Anthony R. Miller,
Jocelyn M. Bush,
Mark van der Linden,
Vincent Magrini,
Richard K. Wilson,
Todd Kitten,
Serina King
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009222
Subject(s) - streptococcus oralis , sialic acid , bacterial adhesin , biology , microbiology and biotechnology , serine , pathogenesis , platelet , biochemistry , bacteria , streptococcus , genetics , immunology , gene , phosphorylation , virulence
Bacterial binding to platelets is a key step in the development of infective endocarditis (IE). Sialic acid, a common terminal carbohydrate on host glycans, is the major receptor for streptococci on platelets. So far, all defined interactions between streptococci and sialic acid on platelets are mediated by serine-rich repeat proteins (SRRPs). However, we identified Streptococcus oralis subsp. oralis IE-isolates that bind sialic acid but lack SRRPs. In addition to binding sialic acid, some SRRP - isolates also bind the cryptic receptor β-1,4-linked galactose through a yet unknown mechanism. Using comparative genomics, we identified a novel sialic acid-binding adhesin, here named AsaA ( a ssociated with s ialic acid a dhesion A), present in IE-isolates lacking SRRPs. We demonstrated that S . oralis subsp. oralis AsaA is required for binding to platelets in a sialic acid-dependent manner. AsaA comprises a non-repeat region (NRR), consisting of a FIVAR/CBM and two Siglec-like and Unique domains, followed by 31 DUF1542 domains. When recombinantly expressed, Siglec-like and Unique domains competitively inhibited binding of S . oralis subsp. oralis and directly interacted with sialic acid on platelets. We further demonstrated that AsaA impacts the pathogenesis of S . oralis subsp. oralis in a rabbit model of IE. Additionally, we found AsaA orthologues in other IE-causing species and demonstrated that the NRR of AsaA from Gemella haemolysans blocked binding of S . oralis subsp. oralis , suggesting that AsaA contributes to the pathogenesis of multiple IE-causing species. Finally, our findings provide evidence that sialic acid is a key factor for bacterial-platelets interactions in a broader range of species than previously appreciated, highlighting its potential as a therapeutic target.