The Calcium-induced Conformation and Glycosylation of Scavenger-rich Cysteine Repeat (SRCR) Domains of Glycoprotein 340 Influence the High Affinity Interaction with Antigen I/II Homologs

Purushotham, Sangeetha; Deivanayagam, Champion

doi:10.1074/jbc.m114.565507

Cited by 33 publications

(54 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the same vein, compared to single SRCR domains, three tandem SRCR domains displayed a cooperative increase in their bacterial adherence. 22 …”

Section: Resultsmentioning

confidence: 99%

“…That multiple proteins are being stretched is not surprising as gp340 has the ability to self-associate and form higher order complexes, as large as 5000 kDa. 22 Hence, pulling on one protein would lead to the stretching of self-associated gp340 aggregates. The speculated occurrence of such protein unfolding events is supported by the fact that force peaks were well described with the WLC model (Figure 5b inset).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Binding Forces of Streptococcus mutans P1 Adhesin

Sullan

Crowley

et al. 2015

ACS Nano

View full text Add to dashboard Cite

Streptococcus mutans is a Gram-positive oral bacterium that is a primary etiological agent associated with human dental caries. In the oral cavity, S. mutans adheres to immobilized salivary agglutinin (SAG) contained within the salivary pellicle on the tooth surface. Binding to SAG is mediated by cell surface P1, a multifunctional adhesin that is also capable of interacting with extracellular matrix proteins. This may be of particular importance outside of the oral cavity as S. mutans has been associated with infective endocarditis and detected in atherosclerotic plaque. Despite the biomedical importance of P1, its binding mechanisms are not completely understood. In this work, we use atomic force microscopy-based single-molecule and single-cell force spectroscopy to quantify the nanoscale forces driving P1-mediated adhesion. Single-molecule experiments show that full-length P1, as well as fragments containing only the P1 globular head or C-terminal region, binds to SAG with relatively weak forces (~50 pN). In contrast, single-cell analyses reveal that adhesion of a single S. mutans cell to SAG is mediated by strong (~500 pN) and long-range (up to 6000 nm) forces. This is likely due to the binding of multiple P1 adhesins to self-associated gp340 glycoproteins. Such a cooperative, long-range character of the S. mutans–SAG interaction would therefore dramatically increase the strength and duration of cell adhesion. We also demonstrate, at single-molecule and single-cell levels, the interaction of P1 with fibronectin and collagen, as well as with hydrophobic, but not hydrophilic, substrates. The binding mechanism (strong forces, cooperativity, broad specificity) of P1 provides a molecular basis for its multifunctional adhesion properties. Our methodology represents a valuable approach to probe the binding forces of bacterial adhesins and offers a tractable methodology to assess anti-adhesion therapy.

show abstract

“…In the same vein, compared to single SRCR domains, three tandem SRCR domains displayed a cooperative increase in their bacterial adherence. 22 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Binding Forces of Streptococcus mutans P1 Adhesin

Sullan

Crowley

et al. 2015

ACS Nano

View full text Add to dashboard Cite

show abstract

“…There is evidence that the head (V) regions of SspB, SpaP, and AspA facilitate gp340 binding activity (9,25,32). To determine whether the V domain of BspA plays a similar role in mediating binding to immobilized gp340, anti-V domain antibodies were affinity-purified from ␣-Spy1325mid antiserum (Fig.…”

Section: Distribution Of Agi/ii Polypeptides In Gbs-mentioning

confidence: 99%

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

Rego

Heal

Pidwill

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans. Complementary crystallographic and biophysical characterization of BspA reveal a novel ␤-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections. Streptococcus agalactiae (group B Streptococcus (GBS)4 ) is a commensal of the gastrointestinal tract and part of the normal microbiota of the female rectovaginal tract, where it is carried asymptomatically by ϳ10 -40% of women of childbearing age (1). However, as an opportunistic pathogen, GBS is the leading cause of neonatal meningitis and sepsis in the developed world. The predominant route by which GBS is transmitted to infants is from the mother, either during birth or following breach of the placental barrier in utero. Antenatal GBS screening strategies are therefore commonly used to identify colonized women, who then receive antimicrobial prophylaxis. Nevertheless, GBS remains a major cause of morbidity and mortality in infants worldwide (2).Because maternal GBS colonization is the primary risk factor for vertical transmission of neonatal infection (3), there has been considerable focus on the mechanisms underlying GBS colonization of the female genitourinary (GU) tract. A number of putative colonization determinants have been identified, including the following: ␣C protein, mediating entry of GBS into cervical epithelial cells (4); pili, shown to contribute to vaginal attachment (5); and Srr-1, which binds keratin-4 (5) and fibrinogen (6) on the surface of vaginal epithelium. In addition, GBS expresses numerous extracellular matrix-binding proteins, including C5a peptidase (ScpB) and FbsA, which may promote attachment to mucosal tissues of the GU tract (7).Antigen I/II (AgI/II) family polypeptide adhesins are found widely across the Streptococcus genus and have been best characterized for those streptococci indigenous to the oral cavity (8). In silico analyses have recently revealed the presence of genes encoding AgI/II family polypeptides in GBS, which we have designated here group B Streptococcus surface proteins (Bsp). These proteins conform to a conserved primary structure consisting of seven distinct regions (Fig. 1). The N-terminal region comprises a signal (leader) peptide, an N-terminal domain, and an ...

show abstract

“…The interaction between S. mutans and DMBT1 has been investigated in the context of cariogenesis. DMBT1 induces bacterial aggregation in saliva, leading to the clearance of bacteria from the oral cavity, while DMBT1 in the tooth surface-adsorbed form induces bacterial adherence, leading to bacterial accumulation (Eriksson et al, 2007;Larson et al, 2011;Oho, Yu, Yamashita, & Koga, 1998;Purushotham & Deivanayagam, 2014).…”

mentioning

confidence: 99%

DMBT1 involvement in the human aortic endothelial cell response to Streptococcus mutans

Oho

Nagata

2019

Molecular Oral Microbiology

View full text Add to dashboard Cite

Streptococcus mutans is a causative organism of dental caries and has been reported to be associated with the development of cardiovascular disease (CVD). Previous studies have demonstrated that S. mutans invades human aortic endothelial cells (HAECs) and HAECs invaded by S. mutans produce higher levels of CVD–related cytokines than non‐invaded HAECs. DMBT1 (deleted in malignant brain tumors 1), also known as salivary agglutinin or gp‐340, belongs to the scavenger receptor cysteine–rich superfamily. DMBT1 is expressed in epithelial and non‐epithelial tissues and has multiple functions. The interaction between S. mutans and DMBT1 has been demonstrated in cariogenesis, but DMBT1 involvement in CVD has not been examined. In this study, we investigated DMBT1 expression in HAECs stimulated with S. mutans and examined the role of DMBT1 in the interaction between S. mutans and HAECs. All of the tested S. mutans strains induced higher production levels of DMBT1 in HAECs than those in unstimulated HAECs. More S. mutans cells adhered to DMBT1 knock down HAECs than to DMBT1–producing HAECs. Invasion of DMBT1 knock down HAECs by S. mutans was stronger than that of DMBT1–producing HAECs, and externally added DMBT1 reduced bacterial invasion. Cytokine production by DMBT1 knock down HAECs by S. mutans stimulation was higher than that by DMBT1–producing HAECs. These phenomena seemed to be due to the effect of released DMBT1, namely, the inhibition of bacterial adherence to HAECs by DMBT1. These results suggest that DMBT1 plays a protective role against the S. mutans–induced CVD process in HAECs.

show abstract

The Calcium-induced Conformation and Glycosylation of Scavenger-rich Cysteine Repeat (SRCR) Domains of Glycoprotein 340 Influence the High Affinity Interaction with Antigen I/II Homologs

Cited by 33 publications

References 54 publications

Binding Forces of Streptococcus mutans P1 Adhesin

Binding Forces of Streptococcus mutans P1 Adhesin

Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae

DMBT1 involvement in the human aortic endothelial cell response to Streptococcus mutans

Contact Info

Product

Resources

About