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Streptococcus mutans induces IgA nephropathy-like glomerulonephritis in rats with severe dental caries.

ABSTRACT: The mechanisms underlying immunoglobulin A nephropathy (IgAN), the most common chronic form of primary glomerulonephritis, remain poorly understood. Streptococcus mutans, a Gram-positive facultatively anaerobic oral bacterium, is a common cause of dental caries. In previous studies, S. mutans isolates that express Cnm protein on their cell surface were frequently detected in IgAN patients. In the present study, inoculation of Cnm-positive S. mutans in the oral cavities of 2-week-old specific-pathogen free Sprague-Dawley rats fed a high-sucrose diet for 32 weeks produced severe dental caries in all rats. Immunohistochemical analyses of the kidneys using IgA- and complement C3-specific antibodies revealed positive staining in the mesangial region. Scanning electron microscopy revealed a wide distribution of electron dense deposits in the mesangial region and periodic acid-Schiff staining demonstrated prominent proliferation of mesangial cells and mesangial matrix. These results suggest that IgAN-like glomerulonephritis was induced in rats with severe dental caries by Cnm-positive S. mutans.

SUBMITTER: Naka S

PROVIDER: S-EPMC7952735 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Specific strains of Streptococcus mutans, a pathogen of dental caries, in the tonsils, are associated with IgA nephropathy.

Project description:Streptococcus mutans is known to be a major causative agent of dental caries, and strains expressing the cell surface collagen-binding Cnm protein contribute to the development of several systemic diseases. A relationship between tonsillar immunity and glomerulonephritis has been recognized in IgA nephropathy (IgAN), and specific pathogens may have effects on tonsillar immunity (mucosal immunity). Here, we present findings showing a relationship between the presence of Cnm-positive S. mutans strains in the tonsils of IgAN patients and IgAN condition/pathogenesis. Analyses of tonsillar specimens obtained from patients with IgAN (n = 61) and chronic tonsillitis (controls; n = 40) showed that the Cnm protein-positive rate was significantly higher in IgAN patients. Among IgAN patients, the tonsillar Cnm-positive group (n = 15) had a significantly higher proportion of patients with high urinary protein (>1.5 g/gCr) and lower serum albumin level than the Cnm-negative group (n = 46). Additionally, Cnm protein and CD68, a common human macrophage marker, were shown to be merged in the tonsils of IgAN patients. These findings suggest that Cnm-positive S. mutans strains in the tonsils may be associated with severe IgAN.

| S-EPMC6934739 | biostudies-literature

Presence of Streptococcus mutans strains harbouring the cnm gene correlates with dental caries status and IgA nephropathy conditions.

Project description:Streptococcus mutans is a major pathogen of human dental caries. Strains harbouring the cnm gene, which encodes Cnm, a collagen-binding protein, contribute to the development of several systemic diseases. In this study, we analysed S. mutans strains isolated from the oral cavity of immunoglobulin (Ig)A nephropathy (IgAN) patients to determine potential relationships between cnm and caries status as well as IgAN conditions. Saliva specimens were collected from 109 IgAN patients and the cnm status of isolated S. mutans strains was determined using PCR. In addition, the dental caries status (decayed, missing or filled teeth [DMFT] index) in patients who agreed to dental consultation (n = 49) was evaluated. The DMFT index and urinary protein levels in the cnm-positive group were significantly higher than those in the cnm-negative group (p < 0.05). Moreover, the urinary protein levels in the high DMFT (≥15) group were significantly higher than those in the low DMFT (<15) group (p < 0.05). Our results show that isolation of cnm-positive S. mutans strains from the oral cavity may be associated with urinary protein levels in IgAN patients, especially those with a high dental caries status.

| S-EPMC5095553 | biostudies-literature

<i>Streptococcus mutans-</i>associated bacteria in dental plaque of severe early childhood caries.

Project description:BackgroundStreptococcus mutans (S. mutans) is a potential pathogenic bacteria of dental caries. However, the level of S. mutans is low in some children with severe early childhood caries (SECC).AimTo evaluate the effect of S. mutans level on dental microbiome and cariogenesis.MethodsThe oral microbiota was compared between caries-free group (CF) and SECC group.16S rRNA gene sequencing was used for S. mutans level bacterial community analysis. The candidate bacteria that were closely related with S. mutans abundance were identified and confirmed by absolute quantitative real-time PCR in clinical dental plaque samples from CF and SECC groups.ResultsThrough in-depth analysis of dental plaque microorganism, Leptotrichia, Selenomonas and Prevotella_7 were found in the S. mutans-low group (p < 0.05) and Porphyromonas, Selenomonas_3 were found in the S. mutans-high group (p < 0.05). Through quantitative real-time PCR, Leptotrichia, Selenomonas and Prevotella_7 were identified as the potential biomarkers of SECC when S. mutans was at a low level.ConclusionLeptotrichia, Selenomonas and Prevotella_7 are identified as potential biomarkers in SECC with a low abundance or without S. mutans. Our study may shed light on the understanding of caries occurrence in SECC with low abundance of S. mutans.AbbreviationsS. mutans, Streptococcus mutans; CF, caries-free; SECC, severe early childhood caries; ECC, early childhood caries; rRNA, ribosome RNA; qPCR, Quantitative real-time PCR; OTUs, operational taxonomic units; ANOVA, analysis of variance; LDA, Linear discriminant analysis; LEfSe, Linear discriminant analysis effect size; COG, Groups of proteins; NMDS, Non-MetricMulti-Dimensional Scaling; IL-1β, interleukin -1β; IL-6, interleukin-6; IL-8, interleukin-8; IL-10, interleukin-10.

| S-EPMC8896182 | biostudies-literature

Contribution of Severe Dental Caries Induced by Streptococcus mutans to the Pathogenicity of Infective Endocarditis.

Project description:Streptococcus mutans, a major pathogen of dental caries, is regarded as a causative agent of infective endocarditis (IE), which mainly occurs in patients with underlying heart disease. However, it remains unknown whether severe dental caries that extend to pulp space represent a possible route of infection. In the present study, we evaluated the virulence of S. mutans for IE development using rats with concurrent severe dental caries and heart valve injury. Dental caries was induced in rats through the combination of a caries-inducing diet and the administration of S. mutans into the oral cavity. Then, the heart valves of a subset of rats were injured using a sterile catheter and wire under general anesthesia. The rats were euthanized at various times with various stages of dental caries. The number of teeth affected by dental caries with pulp exposure was increased in the rats in a time-dependent manner. S. mutans was recovered from injured heart tissue, which was mainly observed in rats with higher number of S. mutans bacteria in mandibular bone and a larger number of teeth in which caries extended to pulp. Dental caries was more severe in rats with heart injury than in rats without heart injury. Sequencing analysis targeting 16S rRNA revealed that specific oral bacteria appeared only in rats with heart injury, which may be related to the development of dental caries. Our findings suggest that dental caries caused by the combination of S. mutans infection and sucrose intake may contribute to S. mutans colonization in injured heart tissue.

| S-EPMC7309618 | biostudies-literature

cnm-positive Streptococcus mutans is associated with galactose-deficient IgA in patients with IgA nephropathy.

Project description:The presence of Streptococcus mutans expressing Cnm protein encoded by cnm (cnm-positive S. mutans) in the oral cavity is associated with immunoglobulin A (IgA) nephropathy (IgAN). However, the precise mechanism by which cnm-positive S. mutans is involved in the pathogenesis of IgAN remains unclear. The present study evaluated glomerular galactose-deficient IgA1 (Gd-IgA1) to clarify the association between the presence of cnm-positive S. mutans and glomerular Gd-IgA1 in patients with IgAN. The presence of S. mutans and cnm-positive S. mutans was evaluated by polymerase chain reaction in saliva specimens from 74 patients with IgAN or IgA vasculitis. Immunofluorescent staining of IgA and Gd-IgA1 using KM55 antibody in clinical glomerular tissues was then performed. There was no significant association between the glomerular staining intensity of IgA and the positive rate of S. mutans. However, there was a significant association between the glomerular staining intensity of IgA and the positive rate of cnm-positive S. mutans (P < 0.05). There was also a significant association between the glomerular staining intensity of Gd-IgA1 (KM55) and the positive rate of cnm-positive S. mutans (P < 0.05). The glomerular staining intensity of Gd-IgA1 (KM55) was not associated with the positive rate of S. mutans. These results suggest that cnm-positive S. mutans in the oral cavity is associated with the pathogenesis of Gd-IgA1 in patients with IgAN.

| S-EPMC9980772 | biostudies-literature

Inhibitory and preventive effects of Arnebia euchroma (Royle) Johnst. root extract on Streptococcus mutans and dental caries in rats.

Project description:BackgroundDental caries is one of the prevalent conditions that threaten oral health. Arnebia euchroma (Royle) Johnst. root (AR) extracts exhibit anti-inflammatory, anti-cancer, and antibacterial properties. This study was designed to investigate the antibacterial impact of AR extract on Streptococcus mutans (S. mutans) UA159 and the anti-caries effect on rats.MethodsThe antibacterial activity of AR extract against S. mutans and its biofilm was determined using the bacterial sensitivity test, the biofilm sensitivity test, and the live-dead staining technique. By fluorescently tagging bacteria, the influence of bacterial adhesion rate was determined. Using a rat caries model, the anti-caries efficacy and safety of AR extract were exhaustively investigated in vivo.ResultsAR extract inhibit not only the growth of S. mutans, but also the generation of S. mutans biofilm, hence destroying and eliminating the biofilm. Moreover, AR extract were able to inhibit S. mutans' adherence to saliva-encapsulated hydroxyapatite (HAP). Further, in a rat model of caries, the AR extract is able to greatly reduce the incidence and severity of caries lesions on the smooth surface and pit and fissure of rat molars, while exhibiting excellent biosafety.ConclusionsAR extract exhibit strong antibacterial activity against S. mutans and can lower the incidence and severity of dental cavities in rats. These findings suggest that Arnebia euchroma (Royle) Johnst. could be utilized for the prevention and treatment of dental caries.

| S-EPMC10908817 | biostudies-literature

Baicalein Inhibits <i>Streptococcus mutans</i> Biofilms and Dental Caries-Related Virulence Phenotypes.

Project description:Dental caries, the most common oral disease, is a major public healthcare burden and affects more than three billion people worldwide. The contemporary understanding of the need for a healthy microbiome and the emergence of antimicrobial resistance has resulted in an urgent need to identify compounds that curb the virulence of pathobionts without microbial killing. Through this study, we have demonstrated for the first time that 5,6,7-trihydroxyflavone (Baicalein) significantly downregulates crucial caries-related virulence phenotypes in Streptococcus mutans. Baicalein significantly inhibited biofilm formation by Streptococcus mutans UA159 (MBIC50 = 200 ?M), without significant growth inhibition. Notably, these concentrations of baicalein did not affect the commensal S. gordonii. Strikingly, baicalein significantly reduced cell surface hydrophobicity, autoaggregation and acid production by S. mutans. Mechanistic studies (qRT-PCR) showed downregulation of various genes regulating biofilm formation, surface attachment, quorum sensing, acid production and competence. Finally, we demonstrate the potential translational value of baicalein by reporting synergistic interaction with fluoride against S. mutans biofilms.

| S-EPMC7926557 | biostudies-literature

Identification of glucosyl transferase inhibitors from Psidium guajava against Streptococcus mutans in dental caries.

Project description:Dental caries is a multi factorial disease that starts with microbiological shifts affected by salivary flow, composition, exposure to fluoride, consumption of dietary sugars, and preventive behaviours. The Streptococcus mutans (S. mutans) is an initiator of caries because there is a variety of a virulence factor unique to the bacterium that has been isolated and plays an important role in caries formation. The aim of the present study is to identify the beneficial effect of bioactive compounds in Psidium guajava (P. guajava) and its inhibitory role against S. mutans in dental caries. The methanolic extract was used for analysis of GC-MS for the identification of bioactive compounds. The results confirm the existence of 7 different compounds. The identified bioactive compounds were corynan-17-ol, 18,19-didehydro-10-methyoxy-acetate, Copaene, 3Bicyclo(5.2.0)nonane, 2-methylene-4,8,8-trimethyl-4-vinyl,Azulene,1,2,3a,4,5,6,7-octahydro-1,4-dimethyl-7-methylethenyl) [1R- (1a,3aa',4a',7a')], ?-Caryophyllene, Alloaromadendrene oxide-(1) and Androstan-17-one, 3-ethyl-3-hydroxy-, (5a). The saliva of dental caries during and after treatment of aqueous leaf extract was used for the analysis of bacterial load and determining the activity of Glucosyl transferase (GTF). The result obtained at different time intervals, showed significant decrease (P < 0.01) in the bacterial load of saliva on P. guajava treatment. The molecular docking studies identified the interaction between GTF and the bioactive compounds of P. guajava. The anticariogenic active compounds interacted through active sites of sucrose and inhibit the formation of glucan. The study suggested that it could be maximized the anticariogenic effect of the selected medicinal plant, and further focus is needed to identify the combined plant extract to explore the additional protection against dental caries.

| S-EPMC6435953 | biostudies-literature

Salivary density of Streptococcus mutans and Streptococcus sobrinus and dental caries in children and adolescents with Down syndrome.

Project description:To assess and compare dental caries experience and salivary S. mutans, S. sobrinus, and streptococci counts between groups of Down syndrome and non-Down syndrome children and adolescents.This study included a sample of 30 Down syndrome children and adolescents (G-DS) and 30 age- and sex-matched non-Down syndrome subjects (G-ND). Dental caries experience was estimated by the number of decayed, missing, and filled teeth in the primary dentition and the permanent dentition. Unstimulated whole saliva samples were collected from all participants. The fluorescence in situ hybridization technique was used to identify the presence and counts of the bacteria. The statistical analysis included chi-square, Student's t-test and Spearman's correlation.The G-DS exhibited a significantly higher caries-free rate (p<0.001) and a lower S. mutans salivary density (p<0.001). No significant differences were found in the salivary densities of S. sobrinus or streptococci between the groups (p=0.09 and p=0.21, respectively). The salivary S. mutans or S. sobrinus densities were not associated with dental caries experience in neither group.The reduced dental caries experience observed in this group of Down syndrome children and adolescents cannot be attributed to lower salivary S. mutans densities, as determined with the fluorescence in situ hybridization technique.

| S-EPMC5482247 | biostudies-other

Longitudinal study of dental caries incidence associated with Streptococcus mutans and Streptococcus sobrinus in patients with intellectual disabilities.

Project description:BackgroundMutans streptococci (Streptococcus mutans and S. sobrinus) are considered to be major etiologic agents of dental caries. Using a polymerase chain reaction method, we detected those bacteria from 145 outpatients (6-30 years old) with intellectual disabilities (ID) and their presence was compared with the incidence of dental caries.MethodsPlaque samples were collected from all erupted tooth sites in subjects with a sterile toothbrush. A dental examination was performed to determine the number of decayed and filled teeth (DFT score) in permanent dentition using the WHO caries diagnostic criteria. A Mann-Whitney U-test was employed to compare the caries scores between combinations of the bacteria, and with a Wilcoxon rank test used to compare caries scores between the baseline and after 1 year.ResultsAmong all subjects, S. mutans and S. sobrinus were possessed by 78.7 and 83.5%, respectively, while 13.1% were positive for S. mutans alone, 17.9% for S. sobrinus alone, and 65.6% for both organisms, with 3.4% were negative for both. The mean DFT score of subjects positive for both S. mutans and S. sobrinus at after 1 year was significantly higher than that of those positive for S. mutans alone (P < 0.01). The increase in caries increment was also significantly greater in subjects with both bacteria detected (P < 0.001).ConclusionOur results indicate that patients with ID harboring both S. mutans and S. sobrinus have a significantly higher incidence of dental caries than those with S. mutans alone.

| S-EPMC4557917 | biostudies-literature

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