scholarly journals In Vivo Colonization with Candidate Oral Probiotics Attenuates Colonization and Virulence of Streptococcus mutans

2020 ◽  
Author(s):  
David. J. Culp ◽  
William Hull ◽  
Matthew J. Bremgartner ◽  
Todd A. Atherly ◽  
Kacey N. Christian ◽  
...  
Keyword(s):  
Dental Caries ◽  
Mouse Model ◽  
Streptococcus Mutans ◽  
Arginine Deiminase ◽  
Oral Streptococci ◽  
Study Results ◽  
Autochthonous Bacteria ◽  
High Sucrose

A collection of 113 Streptococcus strains from supragingival dental plaque of caries-free individuals were recently tested in vitro for direct antagonism of the dental caries pathogen Streptococcus mutans, and for their capacity for arginine catabolism via the arginine deiminase system (ADS). To advance their evaluation as potential probiotics, twelve strains of commensal oral streptococci with various antagonistic and ADS potentials were assessed in a mouse model for oral (i.e., oral mucosal pellicles and saliva) and dental colonization under four diets (healthy or high-sucrose, with or without prebiotic arginine). Colonization by autochthonous bacteria was also monitored. One strain failed to colonize, whereas oral colonization by the other eleven strains varied by 3 log units. Dental colonization was high for five strains regardless of diet, six strains increased colonization with at least one high-sucrose diet, and added dietary arginine decreased dental colonization of two strains. Streptococcus sp. A12 (high in vitro ADS activity and antagonism) and two engineered mutants lacking the ADS (ΔarcADS) or pyruvate oxidase-mediated H2O2 production (ΔspxB) were tested for competition against S. mutans UA159. A12 wild type and ΔarcADS colonized only transiently, whereas ΔspxB persisted, but without altering oral or dental colonization by S. mutans. In testing four additional candidates, S. sanguinis BCC23 markedly attenuated S. mutans’ oral and dental colonization, enhanced colonization of autochthonous bacteria, and decreased severity of smooth surface caries under highly cariogenic conditions. Results demonstrate the utility of the mouse model to evaluate potential probiotics, revealing little correlation between in vitro antagonism and competitiveness against S. mutans in vivo. IMPORTANCE Our results demonstrate in vivo testing of potential oral probiotics can be accomplished and can yield information to facilitate the ultimate design and optimization of novel anti-caries probiotics. We show human oral commensals associated with dental health are an important source of potential probiotics that may be used to colonize patients under dietary conditions of highly varying cariogenicity. Assessment of competitiveness against dental caries pathogen Streptococcus mutans and impact on caries identified strains or genetic elements for further study. Results also uncovered strains that enhanced oral and dental colonization by autochthonous bacteria when challenged with S. mutans, suggesting cooperative interactions for future elucidation. Distinguishing a rare strain that effectively compete with S. mutans under conditions that promote caries further validates our systematic approach to more critically evaluate probiotics for use in humans.

scholarly journals Symbiotic Relationship between Streptococcus mutans and Candida albicans Synergizes Virulence of Plaque BiofilmsIn Vivo

2014 ◽  
Vol 82 (5) ◽  
pp. 1968-1981 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
Punsiri M. Colonne ◽  
Kathleen Scott-Anne ◽  
Stacy Gregoire ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Bacterial Pathogen ◽  
Single Species ◽  
Content Type ◽  
3 Dimensional ◽  
Biofilm Development

ABSTRACTStreptococcus mutansis often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC).S. mutansmay not act alone;Candida albicanscells are frequently detected along with heavy infection byS. mutansin plaque biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhancedin vitroandin vivo. The presence ofC. albicansaugments the production of exopolysaccharides (EPS), such that cospecies biofilms accrue more biomass and harbor more viableS. mutanscells than single-species biofilms. The resulting 3-dimensional biofilm architecture displays sizeableS. mutansmicrocolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction for the pathogenesis of dental caries. Coinfected animals displayed higher levels of infection and microbial carriage within plaque biofilms than animals infected with either species alone. Furthermore, coinfection synergistically enhanced biofilm virulence, leading to aggressive onset of the disease with rampant carious lesions. Ourin vitrodata also revealed that glucosyltransferase-derived EPS is a key mediator of cospecies biofilm development and that coexistence withC. albicansinduces the expression of virulence genes inS. mutans(e.g.,gtfB,fabM). We also found thatCandida-derived β1,3-glucans contribute to the EPS matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding and activity. Altogether, we demonstrate a novel mutualistic bacterium-fungus relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.

scholarly journals Amino Sugars Modify Antagonistic Interactions between Commensal Oral Streptococci andStreptococcus mutans

2019 ◽  
Author(s):  
Lulu Chen ◽  
Brinta Chakraborty ◽  
Jing Zou ◽  
Robert A. Burne ◽  
Lin Zeng
Keyword(s):  
Streptococcus Mutans ◽  
Ex Vivo ◽  
Arginine Deiminase ◽  
Clinical Isolates ◽  
Amino Sugars ◽  
Oral Streptococci ◽  
Streptococcus Gordonii ◽  
Oral Biofilms ◽  
Low Passage

ABSTRACTN-acetylglucosamine (GlcNAc) and glucosamine (GlcN) enhance the competitiveness of the laboratory strain DL1 ofStreptococcus gordoniiagainst the caries pathogenStreptococcus mutans. Here we examine how amino sugars affect the interaction of five low-passage clinical isolates of abundant commensal streptococci withS. mutansutilizing a dual-species biofilm model. Compared to glucose, growth on GlcN or GlcNAc significantly reduced the viability ofS. mutansin co-cultures with most commensals, shifting the proportions of species. Consistent with these results, production of H2O2was increased in most commensals when growing on amino sugars, and inhibition ofS. mutansbyStreptococcus cristatus, Streptococcus oralis,orS. gordoniiwas enhanced by amino sugars on agar plates. All commensals exceptS. oralishad higher arginine deiminase activities when grown on GlcN, and in some cases GlcNAc. Inex vivobiofilms formed using pooled cell-containing saliva (CCS), the proportions ofS. mutanswere drastically diminished when GlcNAc was the primary carbohydrate. Increased production of H2O2could account in large part for the inhibitory effects of CCS biofilms. Surprisingly, amino sugars appeared to improve mutacin production byS. mutanson agar plates, suggesting that the commensals have mechanisms to actively subvert antagonism byS. mutansin co-cultures. Collectively, these findings demonstrate that amino sugars can enhance the beneficial properties of low-passage commensal oral streptococci and highlight their potential for moderating the cariogenicity of oral biofilms.SIGNIFICANCEDental caries is driven by dysbiosis of oral biofilms in which dominance by acid-producing and acid-tolerant bacteria results in loss of tooth mineral. Our previous work demonstrated the beneficial effects of amino sugars, GlcNAc and GlcN, in promoting the antagonistic properties of a health-associated oral bacterium,Streptococcus gordonii,in competition with the major caries pathogenStreptococcus mutans.Here we investigated 5 low-passage clinical isolates of the most common streptococcal species to establish how amino sugars may influence the ecology and virulence of oral biofilms. Using multiplein vitromodels, including a human saliva-derived microcosm biofilm, experiments showed significant enhancement by at least one amino sugar in the ability of most of these bacteria to suppress the caries pathogen. Therefore, our findings demonstrated the mechanism of action by which amino sugars may affect human oral biofilms to promote health.

ACTIVITY OF PERICARP EXTRACT OF MANGOSTEEN AGAINST ORAL STREPTOCOCCI

2017 ◽  
Vol 20 (1) ◽  
pp. 41-46
Author(s):  
Dewi Nurul Mustaqimah ◽  
Josh Erry HW
Keyword(s):  
Antimicrobial Activity ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
World Health ◽  
Direct Result ◽  
Oral Streptococci ◽  
Oral Pathogens

The increasing prevalence of dental caries is still as a major world health problem. Caries is the direct result of acid production by cariogenic oral pathogens, especially Streptococcus mutans. New and better antimicrobial agents active against cariogenic bacteria with minimal side effects on the oral tissues are much needed, especially natural agents derived directly from plants. Phytochemical studies have shown that the extracts from various parts of mangosteen or Garciniamangostana Linn tree contain varieties of secondary metabolites such as prenylated and oxygenated xanthones, many of which have been found in vitro to have antimicrobial properties against oral pathogens. Several studies which examined the eficacy of herbal for human health have shown that xanthones from mangosteen have remarkable biological activities such as antioxidant, antimicrobial, anticancer etc, and had no cytotoxic effects on human gingival fibroblasts. Their results showed that among these xanthone derivatives obtain from pericarp extract of mangosteen, α-mangostin has the most potent antimicrobial activity against cariogenic Streptococcus mutans. It can be concluded that the strong antimicrobial activity of the pericarp extract of mangosteen is a good drug of choice that might be helpful in preventing the dental caries.

Atividade antimicrobiana e antibiofilme da imunoglobulina Y: uma revisão de literatura

2020 ◽  
Vol 9 (12) ◽  
pp. e42291211215
Author(s):  
Fernanda Haboski da Silva ◽  
Gabriela da Luz Machado ◽  
Patricia Kolling Marquezan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Salmonella Spp

A imunoglobulina Y (IgY), termo utilizado para referir-se ao principal anticorpo sérico em galinhas e presente em grande quantidade na gema do ovo, tem se mostrado altamente relevante no meio científico nas últimas décadas. Estudos recentes têm avançado ao estudar a relação da imunoglobulina com atuações antimicrobiana e antibiofilme. Sendo assim, o objetivo do presente estudo é analisar aspectos estruturais e funcionais da imunoglobulina Y bem como sua atividade antimicrobiana e antibiofilme. Para isso, foi realizada uma busca nas bases de dados PubMed/MEDLINE, Cochrane e EMBASE, utilizando os descritores MeSH/DeCS “Dental caries”, “IgY” e seus derivados, associados entre si pelo operador booleano “AND” e adaptados para cada base de dados. Além disso, foi feita uma busca complementar no Google Acadêmico e nas referências dos artigos selecionados. Após uma leitura crítica de títulos e resumos, 10 estudos foram selecionados. A revisão inclui estudos publicados nos últimos 20 anos. A imunoglobulina Y além de apresentar um potencial uso em tratamentos odontológicos, mostrou-se eficiente quanto à redução de patógenos como a Salmonella spp e Pseudomonas aeruginosa. Na cavidade oral, a imunoglobulina apresentou atuação seletiva para com a bactéria Streptococcus mutans. Entretanto, não há um consenso na literatura sobre a ação da IgY na candidíase, doenças nutricionais e metabólicas, neoplasias, amigdalite e o resfriado comum. Assim sendo, a imunoglobulina Y apresenta uma boa atuação antimicrobiana in vitro e in vivo em bactérias do biofilme, porém são necessários mais estudos a fim de elucidar sua ação contra outras bactérias e a aplicabilidade clínica da mesma.

scholarly journals Novel Antibiofilm Chemotherapy Targets Exopolysaccharide Synthesis and Stress Tolerance in Streptococcus mutans To Modulate Virulence ExpressionIn Vivo

2012 ◽  
Vol 56 (12) ◽  
pp. 6201-6211 ◽  
Author(s):  
Megan L. Falsetta ◽  
Marlise I. Klein ◽  
José A. Lemos ◽  
Bruno B. Silva ◽  
Senyo Agidi ◽  
...  
Keyword(s):  
Dental Caries ◽  
Streptococcus Mutans ◽  
Positive Control ◽  
Sprague Dawley ◽  
Content Type ◽  
Treatment Regimens ◽  
Novel Target ◽  
Underlying Mechanisms

ABSTRACTFluoride is the mainstay of dental caries prevention, and yet current applications offer incomplete protection and may not effectively address the infectious character of the disease. Therefore, we evaluated the effectiveness of a novel combination therapy (CT; 2 mM myricetin, 4 mMtt-farnesol, 250 ppm of fluoride) that supplements fluoride with naturally occurring, food-derived, antibiofilm compounds. Treatment regimens simulating those experienced clinically (twice daily for ≤60 s) were used bothin vitroover a saliva-coated hydroxyapatite biofilm model andin vivowith a rodent model of dental caries. The effectiveness of CT was evaluated based on the incidence and severity of carious lesions (compared to fluoride or vehicle control). We found that CT was superior to fluoride (positive control,P< 0.05); topical applications dramatically reduced caries development in Sprague-Dawley rats, all without altering theStreptococcus mutansor total populations within the plaque. We subsequently identified the underlying mechanisms through which applications of CT modulate biofilm virulence. CT targets expression of keyStreptococcus mutansgenes during biofilm formationin vitroandin vivo. These are associated with exopolysaccharide matrix synthesis (gtfB) and the ability to tolerate exogenous stress (e.g.,sloA), which are essential for cariogenic biofilm assembly. We also identified a unique gene (SMU.940) that was severely repressed and may represent a potentially novel target; its inactivation disrupted exopolysaccharide accumulation and matrix development. Altogether, CT may be clinically more effective than current anticaries modalities, targeting expression of bacterial virulence associated with pathogenesis of the disease. These observations may have relevance for development of enhanced therapies against other biofilm-dependent infections.

scholarly journals The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains ofEscherichia coli

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Typhaine Billard-Pomares ◽  
Olivier Clermont ◽  
Miguel Castellanos ◽  
Fatma Magdoud ◽  
Guilhem Royer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Arginine Deiminase ◽  
Epidemiological Surveillance ◽  
Trade Off ◽  
Content Type ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Extended Spectrum

ABSTRACTWe previously identified an operon involved in an arginine deiminase (ADI) pathway (arcoperon) on a CTX-M-producing plasmid from an O102-ST405 strain ofEscherichia coli. As the ADI pathway was shown to be involved in the virulence of various Gram-positive bacteria, we tested whether the ADI pathway could be involved in the epidemiological success of extended-spectrum-β-lactamase (ESBL)-producingE. colistrains. We studied two collections of humanE. coliisolated in France (n = 493) and England (n = 1,509) and show that the prevalence of thearcoperon (i) is higher in ESBL-producing strains (12.1%) than in nonproducers (2.5%), (ii) is higher in CTX-M-producing strains (16%) than in other ESBL producers (3.5%), and (iii) increased over time in ESBL-producing strains from 0% before 2000 to 43.3% in 2011 to 2012. Thearcoperon, found in strains from various phylogenetic backgrounds, is carried by IncF plasmids (85%) or chromosomes (15%) in regions framed by numerous insertion sequences, indicating multiple arrivals. Competition experiments showed that thearcoperon enhances fitness of the strainin vitroin lysogeny broth with arginine.In vivocompetition experiments showed that thearcoperon is advantageous for the strain in a mouse model of urinary tract infection (UTI), whereas it is a burden in a mouse model of intestinal colonization. In summary, we have identified a trait linked to CTX-M-producing strains that is responsible for a trade-off between two mainE. colilifestyles, UTI and gut commensalism. This trait alone cannot explain the wide spread of ESBLs inE. colibut merits epidemiological surveillance.

scholarly journals Multi-Omics Reveals the Inhibition of Lactiplantibacillus plantarum CCFM8724 in Streptococcus mutans-Candida albicans Mixed-Species Biofilms

2021 ◽  
Vol 9 (11) ◽  
pp. 2368
Author(s):  
Qiuxiang Zhang ◽  
Jiaxun Li ◽  
Wenwei Lu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candida Albicans ◽  
Dental Caries ◽  
Streptococcus Mutans ◽  
Biofilm Formation ◽  
Metabolic Reprogramming ◽  
Mixed Species ◽  
Carbohydrate Utilization

Lactiplantibacillus plantarum CCFM8724 is a probiotic with the potential to prevent dental caries in vitro and in vivo. To explore the effects of this probiotic at inhibiting Streptococcus mutans-Candida albicans mixed-species biofilm and preventing dental caries, multi-omics, including metabolomics and transcriptomics, was used to investigate the regulation of small-molecule metabolism during biofilm formation and the gene expression in the mixed-species biofilm. Metabolomic analysis revealed that some carbohydrates related to biofilm formation, such as sucrose, was detected at lower levels due to the treatment with the L. plantarum supernatant. Some sugar alcohols, such as xylitol and sorbitol, were detected at higher levels, which may have inhibited the growth of S. mutans. In transcriptomic analysis, the expression of the virulence genes of C. albicans, such as those that code agglutinin-like sequence (Als) proteins, was affected. In addition, metabolomics coupled with a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and RNA-seq revealed that the L. plantarum supernatant had an active role in sugar metabolism during the formation of the S. mutans-C. albicans mixed-species biofilm, and the L. plantarum supernatant was also related to carbohydrate utilization, glucan biosynthesis, and mycelium formation. Hence, L. plantarum CCFM8724 decreased the mixed-species biofilm mass from the perspective of gene expression and metabolic reprogramming. Our results provide a rationale for evaluating L. plantarum CCFM8724 as a potential oral probiotic for inhibiting cariogenic pathogen biofilm formation and improving dental caries.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cdk Inhibitors ◽  
Comprehensive Overview ◽  
P53 Expression ◽  
Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

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