scholarly journals Protective Immunity against Streptococcus mutansInfection in Mice after Intranasal Immunization with the Glucan-Binding Region of S. mutansGlucosyltransferase

1999 ◽  
Vol 67 (12) ◽  
pp. 6543-6549 ◽  
Author(s):  
Christina Jespersgaard ◽  
George Hajishengallis ◽  
Yan Huang ◽  
Michael W. Russell ◽  
Daniel J. Smith ◽  
...  
Keyword(s):  
Dental Caries ◽  
Immunoglobulin A ◽  
Chimeric Protein ◽  
Infection Model ◽  
Protective Effects ◽  
Oral Streptococci ◽  
Caries Activity ◽  
Mouse Infection Model ◽  
Carious Lesions ◽  
Insoluble Glucan

ABSTRACT Here we present the construction and characterization of a chimeric vaccine protein combining the glucan-binding domain (GLU) of thegtfB-encoded water-insoluble glucan-synthesizing glucosyltransferase enzyme (GTF-I) from Streptococcus mutans and thioredoxin from Escherichia coli, which increases the solubility of coexpressed recombinant proteins and stimulates proliferation of murine T cells. The protective potential of intranasal (i.n.) immunization with this chimeric immunogen was compared to that of the GLU polypeptide alone in a mouse infection model. Both immunogens were able to induce statistically significant mucosal (salivary and vaginal) and serum responses (P < 0.01) which were sustained to the end of the study (experimental day 100). Following infection with S. mutans, sham-immunized mice maintained high levels of this cariogenic organism (∼60% of the total oral streptococci) for at least 5 weeks. In contrast, animals immunized with the thioredoxin-GLU chimeric protein (Thio-GLU) showed significant reduction (>85%) inS. mutans colonization after 3 weeks (P < 0.05). The animals immunized with GLU alone required 5 weeks to demonstrate significant reduction (>50%) of S. mutansinfection (P < 0.05). Evaluation of dental caries activity at the end of the study showed that mice immunized with either Thio-GLU or GLU had significantly fewer carious lesions in the buccal enamel or dentinal surfaces than the sham-immunized animals (P < 0.01). The protective effects against S. mutans colonization and caries activity following i.n. immunization with GLU or Thio-GLU are attributed to the induced salivary immunoglobulin A (IgA) anti-GLU responses. Although in general Thio-GLU was not significantly better than GLU alone in stimulating salivary IgA responses and in protection against dental caries, the finding that the GLU polypeptide alone, in the absence of any immunoenhancing agents, is protective against disease offers a promising and safe strategy for the development of a vaccine against caries.

Immunization with Dextransucrases, Levansucrases, and Glycosidic Hydrolases from Oral Streptococci. II. Immunization with Glucosyltransferases, Fructosyltransferases, and Glycosidic Hydrolases from Oral Streptococci in Monkeys

1977 ◽  
Vol 56 (12) ◽  
pp. 1586-1598 ◽  
Author(s):  
Arthur N. Bahn ◽  
Irving L. Shklair ◽  
James A. Hayashi
Keyword(s):  
Dental Caries ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Control Group ◽  
Oral Streptococci ◽  
Primate Model ◽  
Pathological Effect ◽  
Carious Lesions ◽  
Gross Lesions

The feasibility of immunizing monkeys with enzymes from oral streptococci in an attempt to reduce dental caries was investigated. Forty rhesus monkeys, Macaca mulatta, were used. Cariogenic streptococci, S mutans, were implanted into all the monkeys' mouths. There was no pathological effect resulting from immunization. Of the 40 animals, 30 retained the implanted flora throughout the experiment; the remaining 10 were reimplanted until the streptococci remained. In six months, gross carious lesions were evident with plaque. Inhibitors present in the monkey sera after immunization inhibited glucosyltransferase, fructosyltransferase, and neuraminidase activzties. It was presumed the inhibitors were antibodies. There was a reduction of 68.6% in the total carious lesions in the animals immunized intraorally with glucosyltransferase, 62.4% reduction in those injected with fructosyltransferase, and 57.4% reduction in total lesions in those immunized with glycosidic hydro lases after 19 months, as compared to the control group. There were no gross lesions apparent in the group immunized with glycosidic hydrolases. It appears that immunization with enzymes significantly reduces caries and is feasible in a primate model.

Effect of the Contraceptive Steroids Norethynodrel and Mestranol on Dental Caries Activity in Young Adult Female Rats

1973 ◽  
Vol 52 (4) ◽  
pp. 753-757 ◽  
Author(s):  
F.T.Y. Liu ◽  
H.S. Lin
Keyword(s):  
Young Adult ◽  
Dental Caries ◽  
Adult Female ◽  
Female Rats ◽  
Test Diet ◽  
Caries Activity ◽  
Contraceptive Steroids ◽  
Carious Lesions

Norethynodrel and mestranol in a ratio identical to that used for contraception were injected subcutaneously daily for five weeks into young adult female rats. These rats were fed with a purified caries test diet. The carious lesions of the treated rats increased proportionately with increased doses of the agents.

Therapeutic Vaccine against Streptococcus sobrinus-induced Caries

2004 ◽  
Vol 83 (4) ◽  
pp. 354-358 ◽  
Author(s):  
M. Dinis ◽  
D. Tavares ◽  
A.J.M.M. Fonseca ◽  
R. Faria ◽  
A. Ribeiro ◽  
...  
Keyword(s):  
Dental Caries ◽  
Immunoglobulin A ◽  
Therapeutic Vaccine ◽  
Protective Effects ◽  
Streptococcus Sobrinus ◽  
Safe Strategy ◽  
Early Production ◽  
Ad Libitum ◽  
Caries Lesions ◽  
Salivary Immunoglobulin A

Streptococcus sobrinus produces a virulence-associated immunomodulatory protein (VIP) which suppresses the host-specific immune response and induces the early production of IL-10. In this study, we evaluated the effects of therapeutic immunization with this VIP on the incidence of caries in S. sobrinus-infected rats. Groups of Wistar rats were orally infected with S. sobrinus and fed with sucrose-sweetened drinking water ad libitum. Five days later, rats were immunized intranasally with active or heat-inactivated VIP plus alum as adjuvant or PBS plus adjuvant (sham-immunized). After 3 wks, all rats were re-immunized as above. Evaluation of dental caries showed that VIP-immunized animals had significantly fewer enamel sulcal and proximal caries lesions than did the sham-immunized animals (p < 0.001). The protective effects following therapeutic VIP immunization were attributed to the induced salivary immunoglobulin A specific to the VIP. These results offer a promising and safe strategy for the development of a vaccine against dental caries.

scholarly journals An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lucie Jelínková ◽  
Hugo Jhun ◽  
Allison Eaton ◽  
Nikolai Petrovsky ◽  
Fidel Zavala ◽  
...  
Keyword(s):  
Mouse Model ◽  
Malaria Vaccine ◽  
High Titer ◽  
Circumsporozoite Protein ◽  
Infection Model ◽  
Vaccine Platform ◽  
Junctional Region ◽  
Mouse Infection Model ◽  
Virus Like Particle ◽  
Major Surface

AbstractA malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.

scholarly journals sCD14 Level in Saliva of Children and Adolescents with and without Dental Caries, a Hurdle Model

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 679
Author(s):  
Gaia Pellegrini ◽  
Marcello Maddalone ◽  
Matteo Malvezzi ◽  
Marilisa Toma ◽  
Massimo Del Fabbro ◽  
...  
Keyword(s):  
Dental Caries ◽  
Innate Immune ◽  
Hurdle Model ◽  
Soluble Cd14 ◽  
Clear Cut ◽  
Carious Lesions ◽  
Decayed Tooth ◽  
Group A ◽  
The Relationship ◽  
Control Study

Objective: Soluble CD14 (sCD14) plays an important role in the innate immune response of the oral cavity. The investigation of this biomarker for detection of carious lesions is an even more actual procedure due to its non-invasiveness and the ease of withdrawal. The purpose of the present observational case-control study was to evaluate whether the quantification of sCD14 in children and adolescent’s saliva can discriminate healthy subjects from those suffering from tooth decay. Materials and Methods: 164 subjects (6 to 17 years) were selected and divided into 2 groups: those with at least 1 decayed tooth were assigned to group Decayed (n = 82) and those free from dental caries to group Healthy (n = 82). The amount of salivary soluble CD14 was quantified. Results: Mean salivary soluble CD14 was 28.3 ± 10.8 μg/mL in the Healthy group and 22 ± 9.6 μg/mL in the Decayed group. A hurdle model was applied to the data to estimate both the probability of having carious lesions and their number in relation to sCD14 levels. sCD14 was strongly associated (p < 0.01) with an inverse relation to both the probability of having caries and their number (falling rate of 5% per unit CD14 μg/mL). Conclusions: This data confirms the relationship between sCD14 and the presence of dental caries. However, there is no clear cut off level between healthy and unhealthy subjects, so it is currently not possible to use sCD14 as a biomarker to determine the risk of decays.

Modulatory Effect of Glycated Collagen on Oral Streptococcal Nanoadhesion

2020 ◽  
Vol 100 (1) ◽  
pp. 82-89
Author(s):  
C.M.A.P. Schuh ◽  
B. Benso ◽  
P.A. Naulin ◽  
N.P. Barrera ◽  
L. Bozec ◽  
...  
Keyword(s):  
Dental Caries ◽  
Biofilm Formation ◽  
Type I Collagen ◽  
Type I ◽  
Oral Streptococci ◽  
Oral Diseases ◽  
Collagen Crosslinking ◽  
Initial Adhesion ◽  
Collagen Glycation ◽  
The Impact

Biofilm-mediated oral diseases such as dental caries and periodontal disease remain highly prevalent in populations worldwide. Biofilm formation initiates with the attachment of primary colonizers onto surfaces, and in the context of caries, the adhesion of oral streptococci to dentinal collagen is crucial for biofilm progression. It is known that dentinal collagen suffers from glucose-associated crosslinking as a function of aging or disease; however, the effect of collagen crosslinking on the early adhesion and subsequent biofilm formation of relevant oral streptococci remains unknown. Therefore, the aim of this work was to determine the impact of collagen glycation on the initial adhesion of primary colonizers such as Streptococcus mutans UA159 and Streptococcus sanguinis SK 36, as well as its effect on the early stages of streptococcal biofilm formation in vitro. Type I collagen matrices were crosslinked with either glucose or methylglyoxal. Atomic force microscopy nanocharacterization revealed morphologic and mechanical changes within the collagen matrix as a function of crosslinking, such as a significantly increased elastic modulus in crosslinked fibrils. Increased nanoadhesion forces were observed for S. mutans on crosslinked collagen surfaces as compared with the control, and retraction curves obtained for both streptococcal strains demonstrated nanoscale unbinding behavior consistent with bacterial adhesin-substrate coupling. Overall, glucose-crosslinked substrates specifically promoted the initial adhesion, biofilm formation, and insoluble extracellular polysaccharide production of S. mutans, while methylglyoxal treatment reduced biofilm formation for both strains. Changes in the adhesion behavior and biofilm formation of oral streptococci as a function of collagen glycation could help explain the biofilm dysbiosis seen in older people and patients with diabetes. Further studies are necessary to determine the influence of collagen crosslinking on the balance between acidogenic and nonacidogenic streptococci to aid in the development of novel preventive and therapeutic treatment against dental caries in these patients.

scholarly journals Repurposing Napabucasin as an Antimicrobial Agent against Oral Streptococcal Biofilms

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xinyi Kuang ◽  
Tao Yang ◽  
Chenzi Zhang ◽  
Xian Peng ◽  
Yuan Ju ◽  
...  
Keyword(s):  
Dental Caries ◽  
Laser Scanning ◽  
Antibacterial Activities ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Oral Streptococci ◽  
Oral Keratinocytes ◽  
Microbial Composition ◽  
Biofilm Inhibition ◽  
Multispecies Biofilms

Objectives. Disruption of microbial biofilms is an effective way to control dental caries. Drug resistance and side effects of the existing antimicrobials necessitate the development of novel antibacterial agents. The current study was aimed at investigating the antibacterial activities of the repurposed natural compound napabucasin against oral streptococci. Methods. The minimum inhibitory concentration, minimum bactericidal concentration, minimum biofilm inhibition concentration, and minimum biofilm reduction concentration of Streptococcus mutans, Streptococcus gordonii, and Streptococcus sanguinis were examined by a microdilution method. Cytotoxicity of napabucasin against human oral keratinocytes, human gingival epithelia, and macrophage RAW264.7 was evaluated by CCK8 assays. The dead/live bacterium and exopolysaccharide in the napabucasin-treated multispecies biofilms were evaluated by confocal laser scanning microscopy. Microbial composition within the napabucasin-treated biofilms was further visualized by fluorescent in situ hybridization and qPCR. And the cariogenicity of napabucasin-treated biofilms was evaluated by transverse microradiography. Results. Napabucasin exhibited good antimicrobial activity against oral streptococcal planktonic cultures and biofilms but with lessened cytotoxicity as compared to chlorhexidine. Napabucasin reduced the cariogenic S. mutans and increased the proportion of the commensal S. gordonii in the multispecies biofilms. More importantly, napabucasin significantly reduced the demineralization capability of biofilms on tooth enamels. Conclusion. Napabucasin shows lessened cytotoxicity and comparable antimicrobial effects to chlorhexidine. Repurposing napabucasin may represent a promising adjuvant for the management of dental caries.

scholarly journals The zinc transporter ZnuABC is critical for the virulence of Chromobacterium violaceum and contributes to diverse zinc-dependent physiological processes

2021 ◽  
Author(s):  
Renato E. R. S. Santos ◽  
Waldir P. da Silva Júnior ◽  
Simone A. Harrison ◽  
Eric P Skaar ◽  
Walter J. Chazin ◽  
...  
Keyword(s):  
Mutant Strain ◽  
Zinc Uptake ◽  
Chromobacterium Violaceum ◽  
Host Protein ◽  
Infection Model ◽  
Uptake System ◽  
Environmental Bacterium ◽  
Mouse Infection Model ◽  
Synthetic Metal

Chromobacterium violaceum is a ubiquitous environmental bacterium that causes sporadic life-threatening infections in humans. How C. violaceum acquires zinc to colonize environmental and host niches is unknown. In this work, we demonstrated that C. violaceum employs the zinc uptake system ZnuABC to overcome zinc limitation in the host, ensuring the zinc supply for several physiological demands. Our data indicated that the C. violaceum ZnuABC transporter is encoded in a zur-CV_RS15045-CV_RS15040-znuCBA operon. This operon was repressed by the zinc uptake regulator Zur and derepressed in the presence of the host protein calprotectin (CP) and the synthetic metal chelator EDTA. A ΔznuCBA mutant strain showed impaired growth under these zinc-chelated conditions. Moreover, the deletion of znuCBA provoked a reduction in violacein production, swimming motility, biofilm formation, and bacterial competition. Remarkably, the ΔznuCBA mutant strain was highly attenuated for virulence in an in vivo mouse infection model and showed a low capacity to colonize the liver, grow in the presence of CP, and resist neutrophil killing. Overall, our findings demonstrate that ZnuABC is essential for C. violaceum virulence, contributing to subvert the zinc-based host nutritional immunity.

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