Streptococcus oralis subsp. dentisani Produces Monolateral Serine-Rich Repeat Protein Fibrils, One of Which Contributes to Saliva Binding via Sialic Acid

• Published in: Infection and immunity Vol. 87; no. 10
• Main Authors: Ronis, Allen, Brockman, Kenneth, Singh, Anirudh K, Gaytán, Meztlli O, Wong, Alexander, McGrath, Sean, Owen, C David, Magrini, Vincent, Wilson, Richard K, van der Linden, Mark, King, Samantha J
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.10.2019
• Subjects: Amino Acid Sequence; Bacterial Adhesion; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Proteins - ultrastructure; Biofilms - growth & development; Endocarditis, Bacterial - microbiology; Endocarditis, Bacterial - pathology; Gene Expression; Humans; Molecular Pathogenesis; Mutation; Protein Binding; Protein Domains; Protein Isoforms - genetics; Protein Isoforms - metabolism; Protein Isoforms - ultrastructure; Saliva - chemistry; Saliva - metabolism; Sialic Acids - chemistry; Sialic Acids - metabolism; Streptococcus oralis - chemistry; Streptococcus oralis - genetics; Streptococcus oralis - metabolism; monolateral fibril; sialic acid; adhesion; biofilms; Streptococcus oralis subsp. dentisani; platelets; serine-rich repeat proteins
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00406-19

Our studies reveal that the oral colonizer and cause of infective endocarditis subsp. displays a striking monolateral distribution of surface fibrils. Furthermore, our data suggest that these fibrils impact the structure of adherent bacterial chains. Mutagenesis studies indicate that these fibrils are dependent on three serine-rich repeat proteins (SRRPs), here named ibril- ssociated rotein (FapA), FapB, and FapC, and that each SRRP forms a different fibril with a distinct distribution. SRRPs are a family of bacterial adhesins that have diverse roles in adhesion and that can bind to different receptors through modular nonrepeat region domains. Amino acid sequence and predicted structural similarity searches using the nonrepeat regions suggested that FapA may contribute to interspecies interactions, that FapA and FapB may contribute to intraspecies interactions, and that FapC may contribute to sialic acid binding. We demonstrate that a mutant was significantly reduced in binding to saliva. We confirmed a role for FapC in sialic acid binding by demonstrating that the parental strain was significantly reduced in adhesion upon addition of a recombinantly expressed, sialic acid-specific, carbohydrate binding module, while the mutant was not reduced. However, mutation of a residue previously shown to be essential for sialic acid binding did not decrease bacterial adhesion, leaving the precise mechanism of FapC-mediated adhesion to sialic acid to be defined. We also demonstrate that the presence of any one of the SRRPs is sufficient for efficient biofilm formation. Similar structures were observed on all infective endocarditis isolates examined, suggesting that this distribution is a conserved feature of this subspecies.