scholarly journals Molecular recognition of sialoglycans by streptococcal Siglec-like adhesins: toward the shape of specific inhibitors

2021 ◽  
Author(s):  
Cristina Di Carluccio ◽  
Alba Silipo ◽  
Roberta Marchetti ◽  
Barbara Ben ◽  
Koichi Fukase ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Molecular Recognition ◽  
Oral Cavity ◽  
Commensal Bacteria ◽  
Streptococcus Gordonii ◽  
Healthy Individuals ◽  
Sialic Acid Binding ◽  
Specific Inhibitors

Streptococcus gordonii and sanguinis, commensal bacteria present in the oral cavity of healthy individuals, upon entry into the bloodstream can become pathogenic, causing infective endocarditis (IE). Sialic acid-binding serine-rich repeat...

scholarly journals Binding of the Streptococcus gordonii DL1 Surface Protein Hsa to the Host Cell Membrane Glycoproteins CD11b, CD43, and CD50

2008 ◽  
Vol 76 (10) ◽  
pp. 4686-4691 ◽  
Author(s):  
Yumiko Urano-Tashiro ◽  
Ayako Yajima ◽  
Eizo Takashima ◽  
Yukihiro Takahashi ◽  
Kiyoshi Konishi
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Surface Protein ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Membrane Glycoproteins ◽  
Host Cell Membrane ◽  
Neuraminidase Treatment ◽  
Sialic Acid Binding

ABSTRACTInfective endocarditis is frequently attributed to oral streptococci. The mechanisms of pathogenesis, however, are not well understood, although interaction between streptococci and phagocytes are thought to be very important. A highly expressed surface component ofStreptococcus gordonii, Hsa, which has sialic acid-binding activity, contributes to infective endocarditis in vivo. In the present study, we found thatS. gordoniiDL1 binds to HL-60 cells differentiated into monocytes, granulocytes, and macrophages. Using a glutathioneS-transferase (GST) fusion to the NR2 domain, which is the sialic acid-binding region of Hsa, we confirmed that the Hsa NR2 domain also binds to differentiated HL-60 cells. To identify which sialoglycoproteins on the surface of differentiated HL-60 cells are receptors for Hsa, intrinsic membrane proteins were assessed by bacterial overlay and far-Western blotting.S. gordoniiDL1 adhered to 100- to 150-kDa proteins, a reaction that was abolished by neuraminidase treatment. These sialoglycoproteins were identified as CD11b, CD43, and CD50 by GST pull-down assay and immunoprecipitation with each specific monoclonal antibody. These data suggest thatS. gordoniiDL1 Hsa specifically binds to three glycoproteins as receptors and that this interaction may be the initial bacterial binding step in infective endocarditis by oral streptococci.

scholarly journals A novel sialic acid-binding adhesin present in multiple species contributes to the pathogenesis of Infective endocarditis

2020 ◽  
Author(s):  
Meztlli O. Gaytán ◽  
Anirudh K. Singh ◽  
Shireen A. Woodiga ◽  
Surina A. Patel ◽  
Seon-Sook An ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Therapeutic Target ◽  
Heart Valves ◽  
Bacterial Species ◽  
Rabbit Model ◽  
Host Factors ◽  
Dependent Manner ◽  
Streptococcus Oralis ◽  
Sialic Acid Binding

AbstractBacterial 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-negative 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 (associated with sialic acid adhesion 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.Authors summaryInfective endocarditis (IE) is typically a bacterial infection of the heart valves that causes high mortality. Infective endocarditis can affect people with preexisting lesions on their heart valves (Subacute-IE). These lesions contain platelets and other host factors to which bacteria can bind. Growth of bacteria and accumulation of host factors results in heart failure. Therefore, the ability of bacteria to bind platelets is key to the development of IE. Here, we identified a novel bacterial protein, AsaA, which helps bacteria bind to platelets and contributes to the development of disease. Although this virulence factor was characterized in Streptococcus oralis, a leading cause of IE, we demonstrated that AsaA is also present in several other IE-causing bacterial species and is likely relevant to their ability to cause disease. We showed that AsaA binds to sialic acid, a terminal sugar present on platelets, thereby demonstrating that sialic acid serves as a receptor for a wider range of IE-causing bacteria than previously appreciated, highlighting its potential as a therapeutic target.

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

2019 ◽  
Vol 87 (10) ◽  
Author(s):  
Allen Ronis ◽  
Kenneth Brockman ◽  
Anirudh K. Singh ◽  
Meztlli O. Gaytán ◽  
Alexander Wong ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Structural Similarity ◽  
Carbohydrate Binding ◽  
Interspecies Interactions ◽  
Content Type ◽  
Streptococcus Oralis ◽  
Bacterial Adhesins ◽  
Protein Fibrils ◽  
Sialic Acid Binding

ABSTRACT Our studies reveal that the oral colonizer and cause of infective endocarditis Streptococcus oralis subsp. dentisani 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 fibril-associated protein A (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 fapC 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 fapC 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 S. oralis subspecies.

scholarly journals Shear-Enhanced Oral Microbial Adhesion

2009 ◽  
Vol 76 (4) ◽  
pp. 1294-1297 ◽  
Author(s):  
Albert M. Ding ◽  
Robert J. Palmer ◽  
John O. Cisar ◽  
Paul E. Kolenbrander
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Streptococcus Gordonii ◽  
Microbial Adhesion

ABSTRACT Shear-enhanced adhesion, although not observed for fimbria-mediated adhesion of oral Actinomyces spp., was noted for Hsa-mediated adhesion of Streptococcus gordonii to sialic acid-containing receptors, an interaction implicated in the pathogenesis of infective endocarditis.

scholarly journals Two Arginine Residues of Streptococcus gordonii Sialic Acid-Binding Adhesin Hsa Are Essential for Interaction to Host Cell Receptors

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154098 ◽  
Author(s):  
Yumiko Urano-Tashiro ◽  
Yukihiro Takahashi ◽  
Riyo Oguchi ◽  
Kiyoshi Konishi
Keyword(s):  
Sialic Acid ◽  
Host Cell ◽  
Streptococcus Gordonii ◽  
Cell Receptors ◽  
Sialic Acid Binding ◽  
Arginine Residues

Streptococcus gordonii promotes rapid differentiation of monocytes into dendritic cells through interaction with the sialic acid-binding adhesin

Odontology ◽  
2011 ◽  
Vol 100 (2) ◽  
pp. 144-148 ◽  
Author(s):  
Yumiko Urano-Tashiro ◽  
Ayako Yajima ◽  
Yukihiro Takahashi ◽  
Kiyoshi Konishi
Keyword(s):  
Dendritic Cells ◽  
Sialic Acid ◽  
Streptococcus Gordonii ◽  
Sialic Acid Binding

scholarly journals A novel sialic acid-binding adhesin present in multiple species contributes to the pathogenesis of Infective endocarditis

2021 ◽  
Vol 17 (1) ◽  
pp. e1009222
Author(s):  
Meztlli O. Gaytán ◽  
Anirudh K. Singh ◽  
Shireen A. Woodiga ◽  
Surina A. Patel ◽  
Seon-Sook An ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Infective Endocarditis ◽  
Rabbit Model ◽  
Dependent Manner ◽  
Bacterial Binding ◽  
Repeat Proteins ◽  
Streptococcus Oralis ◽  
Sialic Acid Binding ◽  
Key Factor ◽  
Multiple Species

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 (associated with sialic acid adhesion 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.

scholarly journals Functional Analysis of the Streptococcus gordonii DL1 Sialic Acid-Binding Adhesin and Its Essential Role in Bacterial Binding to Platelets

2004 ◽  
Vol 72 (7) ◽  
pp. 3876-3882 ◽  
Author(s):  
Yukihiro Takahashi ◽  
Ayako Yajima ◽  
John O. Cisar ◽  
Kiyoshi Konishi
Keyword(s):  
Sialic Acid ◽  
Essential Role ◽  
Signal Sequence ◽  
Complete Removal ◽  
Human Platelets ◽  
Microbial Colonization ◽  
Streptococcus Gordonii ◽  
Rich Region ◽  
Neuraminidase Treatment ◽  
Sialic Acid Binding

ABSTRACT Bacterial recognition of host sialic acid-containing receptors plays an important role in microbial colonization of the human oral cavity. The sialic acid-binding adhesin of Streptococcus gordonii DL1 was previously associated with the hsa gene encoding a 203-kDa protein. The predicted protein sequence consists of an N-terminal nonrepetitive region (NR1), including a signal sequence, a relatively short serine-rich region (SR1), a second nonrepetitive region (NR2), a long serine-rich region (SR2) containing 113 dodecapeptide repeats, and a C-terminal cell wall anchoring domain. In the present study, the contributions of SR1, NR2, and SR2 to Hsa-mediated adhesion were assessed by genetic complementation. Adhesion of an hsa chromosomal deletion mutant to sialic acid-containing receptors was restored by plasmids containing hsa constructs encoding Hsa that lacked either the N- or C-terminal portion of SR2. In contrast, hsa constructs that lacked the coding sequences for SR1, NR2, or the entire SR2 region failed to restore adhesion. Surface expression of recombinant Hsa was not affected by removal of SR1, NR2, or a portion of SR2 but was greatly reduced by complete removal of SR2. Wheat germ agglutinin, a probe for Hsa-specific glycosylation, reacted with recombinant Hsa lacking SR1, NR2, or SR2 but not with recombinant Hsa lacking both SR1 and SR2. Significantly, the aggregation of human platelets by S. gordonii DL1, an interaction implicated in the pathogenesis of infective endocarditis, required the expression of hsa. Moreover, neuraminidase treatment of the platelets eliminated this interaction, further supporting the hypothesis that Hsa plays an essential role in the bacterium-platelet interaction.

scholarly journals Contribution of Sialic Acid-Binding Adhesin to Pathogenesis of Experimental Endocarditis Caused by Streptococcus gordonii DL1

2006 ◽  
Vol 74 (1) ◽  
pp. 740-743 ◽  
Author(s):  
Yukihiro Takahashi ◽  
Eizo Takashima ◽  
Kisaki Shimazu ◽  
Hisao Yagishita ◽  
Takaaki Aoba ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Aortic Valve ◽  
Infection Rate ◽  
Inflammatory Reaction ◽  
Heart Valves ◽  
Streptococcus Gordonii ◽  
Gene Encoding ◽  
Insertional Mutation ◽  
Sialic Acid Binding

ABSTRACT An insertional mutation in hsa, the gene encoding the sialic acid-binding adhesin of Streptococcus gordonii DL1, resulted in a significant reduction of the infection rate of the organism and an inflammatory reaction in the rat aortic valve with experimental endocarditis, suggesting that the adhesin contributes to the infectivity of the organism for heart valves.

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