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1.
J Infect Dis ; 230(Supplement_2): S87-S94, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255395

RESUMO

Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology.


Assuntos
Doença de Alzheimer , Periodontite , Porphyromonas gingivalis , Doença de Alzheimer/microbiologia , Doença de Alzheimer/metabolismo , Humanos , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Disbiose/microbiologia , Infecções Bacterianas/microbiologia , Barreira Hematoencefálica/microbiologia , Animais , Microbiota
2.
J Infect Dis ; 230(Supplement_2): S109-S116, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39255392

RESUMO

Periodontitis is a chronic inflammatory disease driven by dysbiosis in subgingival microbial communities leading to increased abundance of a limited number of pathobionts, including Porphyromonas gingivalis and Treponema denticola. Oral health, particularly periodontitis, is a modifiable risk factor for Alzheimer disease (AD) pathogenesis, with components of both these bacteria identified in postmortem brains of persons with AD. Repeated oral inoculation of mice with P. gingivalis results in brain infiltration of bacterial products, increased inflammation, and induction of AD-like biomarkers. P. gingivalis displays synergistic virulence with T. denticola during periodontitis. The aim of the current study was to determine the ability of P. gingivalis and T. denticola, grown in physiologically relevant conditions, individually and in combination, to induce AD-like pathology following chronic oral inoculation of female mice over 12 weeks. P. gingivalis alone significantly increased all 7 brain pathologies examined: neuronal damage, activation of astrocytes and microglia, expression of inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 6 and production of amyloid-ß plaques and hyperphosphorylated tau, in the hippocampus, cortex and midbrain, compared to control mice. T. denticola alone significantly increased neuronal damage, activation of astrocytes and microglia, and expression of IL-1ß, in the hippocampus, cortex and midbrain, compared to control mice. Coinoculation of P. gingivalis with T. denticola significantly increased activation of astrocytes and microglia in the hippocampus, cortex and midbrain, and increased production of hyperphosphorylated tau and IL-1ß in the hippocampus only. The host brain response elicited by oral coinoculation was less than that elicited by each bacterium, suggesting coinoculation was less pathogenic.


Assuntos
Doença de Alzheimer , Infecções por Bacteroidaceae , Encéfalo , Modelos Animais de Doenças , Porphyromonas gingivalis , Treponema denticola , Animais , Doença de Alzheimer/microbiologia , Doença de Alzheimer/patologia , Camundongos , Feminino , Encéfalo/patologia , Encéfalo/microbiologia , Infecções por Bacteroidaceae/microbiologia , Periodontite/microbiologia , Periodontite/patologia , Microglia/microbiologia , Infecções por Treponema/microbiologia , Infecções por Treponema/patologia , Camundongos Endogâmicos C57BL , Astrócitos/microbiologia , Astrócitos/patologia , Placa Amiloide/patologia , Placa Amiloide/microbiologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Peptídeos beta-Amiloides/metabolismo
3.
Crit Rev Microbiol ; 50(2): 127-137, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36597758

RESUMO

The cause of Alzheimer's disease (AD), and the pathophysiological mechanisms involved, remain major unanswered questions in medical science. Oral bacteria, especially those species associated with chronic periodontitis and particularly Porphyromonas gingivalis, are being linked causally to AD pathophysiology in a subpopulation of susceptible individuals. P. gingivalis produces large amounts of proteolytic enzymes, haem and iron capture proteins, adhesins and internalins that are secreted and attached to the cell surface and concentrated onto outer membrane vesicles (OMVs). These enzymes and adhesive proteins have been shown to cause host tissue damage and stimulate inflammatory responses. The ecological and pathophysiological roles of P. gingivalis OMVs, their ability to disperse widely throughout the host and deliver functional proteins lead to the proposal that they may be the link between a P. gingivalis focal infection in the subgingivae during periodontitis and neurodegeneration in AD. P. gingivalis OMVs can cross the blood brain barrier and may accelerate AD-specific neuropathology by increasing neuroinflammation, plaque/tangle formation and dysregulation of iron homeostasis, thereby inducing ferroptosis leading to neuronal death and neurodegeneration.


Assuntos
Doença de Alzheimer , Periodontite , Humanos , Porphyromonas gingivalis/genética , Adesinas Bacterianas/metabolismo , Periodontite/microbiologia , Ferro
4.
Int J Paediatr Dent ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816920

RESUMO

BACKGROUND: Social disadvantage leads to dental caries during childhood. AIM: This study investigated whether dental caries occur earlier in children from households experiencing social disadvantage than those not experiencing social disadvantage. DESIGN: The overall risk of, and relative time to, early childhood caries (ECC) according to sociodemographic characteristics in Victoria, Australia, was quantified. Records for 134 463 children in Victoria, Australia, from 2009 to 2019 were analysed. Time ratios (TR) and hazard ratios (HR) of carious lesion(s) in early childhood were estimated. RESULTS: Compared with reference groups, Indigenous children had an adjusted TR of 0.80 (95% CI: 0.78, 0.82), children from households with languages other than English had an adjusted TR of 0.83 (95% CI: 0.82, 0.84), and dependants of concession cardholders had an adjusted TR of 0.81 (95% CI: 0.80, 0.81); therefore, 20%, 17% and 19% reduced times to the first carious lesion, respectively. The estimated HRs were 1.57 (95% CI: 1.49, 1.67) for Indigenous children, 1.46 (95% CI: 1.42, 1.50) for children from households with other languages and 1.57 (CI: 1.53, 1.60) for dependants of concession cardholders. CONCLUSION: Preventive oral health interventions must be targeted early in children from households experiencing social disadvantage to avoid social inequities in ECC.

5.
Crit Rev Microbiol ; 48(6): 730-742, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35015598

RESUMO

The human oral microbiome is becoming recognized as playing roles in health and disease well beyond the oral cavity over the lifetime of the individual. The oral microbiome is hypothesized to result from specific colonization events followed by a reproducible and ordered development of complex bacterial communities. Colonization events, proliferation, succession and subsequent community development are dependent on a range of host and environmental factors, most notably the neonate diet. It is now becoming apparent that early childhood and prenatal influences can have long term effects on the development of human oral microbiomes. In this review, the temporal development of the infant human oral microbiome is examined, with the effects of prenatal and postnatal influences and the roles of specific bacteria. Dietary and environmental factors, especially breastfeeding, have a significant influence on the development of the infant oral microbiome. The evidence available regarding the roles and functions of early colonizing bacteria is still limited, and gaps in knowledge where further research is needed to elucidate these specific roles in relation to health and disease still exist.


Assuntos
Microbioma Gastrointestinal , Microbiota , Lactente , Recém-Nascido , Gravidez , Feminino , Humanos , Pré-Escolar , Bactérias/genética , Boca/microbiologia , Aleitamento Materno
6.
Public Health Nutr ; 24(6): 1438-1448, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32718367

RESUMO

OBJECTIVE: To examine associations between childcare type and nutrition and oral health indicators. DESIGN: Cross-sectional data extracted from a longitudinal birth cohort. Parent-completed FFQ and questions regarding oral health and childcare use. The associations between childcare type, classified into four groups: parent care only (PCO), formal childcare only (FCO), informal childcare only (ICO) or combination of care (F&I), and nutrition and oral health indicators were examined. SETTING: Home and childcare. PARTICIPANTS: Families with children aged 3 years (n 273) and 4 years (n 249) in Victoria, Australia. RESULTS: No associations were observed between childcare type and core food/beverage consumption or oral health indicators. For discretionary beverages, compared with children receiving PCO at age 3 years, children in FCO or F&I were less likely to frequently consume fruit juice/drinks (FCO: adjusted OR (AOR) 0·41, 95 % CI 0·17, 0·96, P = 0·04; F&I: AOR 0·32, 95 % CI 0·14, 0·74, P = 0·008). At age 4 years, children receiving FCO or ICO were less likely to consume sweet beverages frequently compared with children receiving PCO: fruit juice/drink (ICO: AOR 0·42, 95 % CI 0·19, 0·94, P = 0·03; FCO: AOR 0·35, 95 % CI 0·14, 0·88, P = 0·03) and soft drink (ICO: AOR 0·23, 95 % CI 0·07, 0·74, P = 0·01; FCO: AOR 0·14, 95 % CI 0·03, 0·76, P = 0·02). CONCLUSIONS: Associations between childcare type and discretionary beverage intake were observed. Investigation into knowledge, attitudes and activities in formal and informal childcare settings is required to explore different health promotion practices that may influence nutrition and oral health.


Assuntos
Cuidado da Criança , Saúde Bucal , Bebidas , Criança , Pré-Escolar , Estudos Transversais , Humanos , Vitória
7.
Biofouling ; 37(7): 767-776, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34425729

RESUMO

Candida albicans causes candidiasis, particularly in immunocompromised patients. Streptococcus salivarius K12 (K12) is a probiotic isolated from a healthy oral cavity. The study aimed to determine the effect of K12 on C. albicans aggregation, biofilm formation and dimorphism. C. albicans ATCC MYA-4901, acquired immunodeficiency syndrome (AIDS) isolate (ALC2), and oral cancer isolate (ALC3) and K12 were used in the study. All C. albicans strains and K12 were grown in yeast peptone dextrose agar and brain heart infusion agar, respectively, prior to aggregation, biofilm and dimorphism assays. Auto-aggregation of C. albicans MYA-4901 and ALC2 was categorised as high, while the co-aggregation of the strains was low in the presence of K12. C. albicans total cell count decreased significantly when co-cultured with K12 compared with monocultured C. albicans biofilm (p < 0.05). Inhibition of yeast-to-hyphae transition was also observed when co-cultured with K12. In conclusion, K12 inhibits C. albicans aggregation, biofilm formation and dimorphism.


Assuntos
Candidíase , Streptococcus salivarius , Biofilmes , Candida albicans , Humanos , Caracteres Sexuais
8.
J Oral Pathol Med ; 49(9): 835-841, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32170981

RESUMO

Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Candida albicans/genética , Carcinogênese/genética , Enzimas Conversoras de Endotelina , Proteínas Fúngicas , Humanos , Neoplasias Bucais/genética
9.
Carcinogenesis ; 40(1): 184-193, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30428016

RESUMO

Microbial infection has been shown to involve in oral carcinogenesis; however, the underlying mechanisms remain poorly understood. The present study aimed to characterize the growth of oral microorganisms as both monospecies and polymicrobial biofilms and determine the effects of their products on oral keratinocytes. Candida albicans (ALC3), Actinomyces naeslundii (AN) and Streptococcus mutans (SM) biofilms or a combination of these (TRI) were grown in flow-cell system for 24 h. The biofilms were subjected to fluorescent in situ hybridization using species-specific probes and analysed using confocal laser scanning microscopy. The effluent derived from each biofilm was collected and incubated with malignant (H357) and normal (OKF6) oral keratinocytes to assess extracellular matrix adhesion, epithelial-mesenchymal transition (EMT) and cytokines expression. Incubation of OKF6 with ALC3 and TRI effluent significantly decreased adhesion of the oral keratinocyte to collagen I, whereas incubation of H357 with similar effluent increased adhesion of the oral keratinocyte to laminin I, significantly when compared with incubation with artificial saliva containing serum-free medium (NE; P < 0.05). In OKF6, changes in E-cadherin and vimentin expression were not consistent with EMT although there was evidence of a mesenchymal to epithelial transition in malignant oral keratinocytes incubated with AN and SM effluent. A significant increase of pro-inflammatory cytokines expression, particularly interleukin (IL)-6 and IL-8, was observed when H357 was incubated with all biofilm effluents after 2- and 24-h incubation when compared with NE (P < 0.05). In conclusion, C.albicans, A.naeslundii and S.mutans form polymicrobial biofilms which differentially modulate malignant phenotype of oral keratinocytes.


Assuntos
Biofilmes , Neoplasias Bucais/patologia , Actinomyces/fisiologia , Candida albicans/fisiologia , Adesão Celular , Células Cultivadas , Citocinas/genética , Transição Epitelial-Mesenquimal , Matriz Extracelular/fisiologia , Genótipo , Humanos , Queratinócitos/fisiologia , Fenótipo , Streptococcus mutans/fisiologia
10.
J Oral Pathol Med ; 48(7): 546-551, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183906

RESUMO

The oral microbiome is composed of microorganisms residing in the oral cavity, which are critical components of health and disease. Disruption of the oral microbiome has been proven to influence the course of oral diseases, especially among immunocompromised patients. Oral microbiome is comprised of inter-kingdom microorganisms, including yeasts such as Candida albicans, bacteria, archaea and viruses. These microorganisms can interact synergistically, mutualistically and antagonistically, wherein the sum of these interactions dictates the composition of the oral microbiome. For instance, polymicrobial interactions can improve the ability of C albicans to form biofilm, which subsequently increases the colonisation of oral mucosa by the yeast. Polymicrobial interactions of C albicans with other members of the oral microbiome have been reported to enhance the malignant phenotype of oral cancer cells, such as the attachment to extracellular matrix molecules (ECM) and epithelial-mesenchymal transition (EMT). Polymicrobial interactions may also exacerbate an inflammatory response in oral epithelial cells, which may play a role in carcinogenesis. This review focuses on the role of polymicrobial interactions between C albicans and other oral microorganisms, including its role in promoting oral carcinogenesis.


Assuntos
Candida albicans , Biofilmes , Carcinogênese , Humanos , Interações Microbianas , Boca
11.
Int J Paediatr Dent ; 29(3): 310-324, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30666740

RESUMO

BACKGROUND: Diet cariogenicity plays a major role as both a protective and risk factor in the development of early childhood caries (ECC). AIM: Develop a scale measuring the cariogenicity of foods and beverages and employ it to describe the cariogenicity of young children's diets and predict dental caries outcomes. DESIGN: Scores of cariogenicity and consumption frequency were applied to food frequency questionnaire (FFQ) collected from an Australian children's cohort study with three time-points of data. One-way ANOVA, with post hoc Tukey test compared mean cariogenic scale measured at 18 months between the subsample of children with caries classification at age 5 years. RESULTS: At 6 months, children's mean cariogenic score was 10.05, increasing to 34.18 at 12 and 50.00 at 18 months. Mean cariogenic scale score at 18 months was significantly higher in children with advanced disease at 5 years (mean scale score: 59.0 ± 15.9) compared to those that were healthy (mean score 47.7 ± 17.5, P = 0.007) or had mild-moderate disease (mean score 48.2 ± 17.3, P = 0.008). CONCLUSIONS: The cariogenic diet scale provides a useful indication of the increasing cariogenicity of children's diets with age and highlights the incorporation of discretionary choice foods and beverages into the diets of young children much earlier than nutritionally recommended.


Assuntos
Cárie Dentária , Dieta Cariogênica , Austrália , Criança , Pré-Escolar , Estudos de Coortes , Dieta , Estudos de Viabilidade , Humanos
12.
J Proteome Res ; 17(7): 2377-2389, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29766714

RESUMO

Porphyromonas gingivalis is an anaerobic, Gram-negative oral pathogen associated with chronic periodontitis. P. gingivalis has an obligate requirement for heme, which it obtains from the host. Heme availability has been linked to disease initiation and progression. In this study we used continuous culture of the bacterium to determine the effect of heme limitation and excess on the P. gingivalis proteome. Four biological replicates of whole cell lysate (WCL) and outer membrane vesicle (OMV) samples were digested with trypsin and analyzed by tandem mass spectrometry and MaxQuant label-free quantification. In total, 1211 proteins were quantified, with 108 and 49 proteins significantly changing in abundance more than 1.5-fold ( p < 0.05) in the WCLs and OMVs, respectively. The proteins most upregulated in response to heme limitation were those involved in binding and transporting heme, whereas the four proteins most upregulated under the heme-excess condition constitute a putative heme efflux system. In general, the protein abundance ratios obtained for OMVs and WCLs agreed, indicating that changes to the OM protein composition are passed onto OMVs; however, 16 proteins were preferentially packaged into OMVs under one condition more than the other. In particular, moonlighting cytoplasmic proteins were preferentially associated with OMVs under heme excess.


Assuntos
Micropartículas Derivadas de Células/química , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Heme/farmacologia , Porphyromonas gingivalis/química , Proteoma/metabolismo , Proteínas da Membrana Bacteriana Externa , Micropartículas Derivadas de Células/efeitos dos fármacos , Heme/análise , Porphyromonas gingivalis/citologia , Porphyromonas gingivalis/ultraestrutura , Proteoma/efeitos dos fármacos
13.
PLoS Pathog ; 11(9): e1005152, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26340749

RESUMO

The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria.


Assuntos
Aminoaciltransferases/metabolismo , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo , Cisteína Endopeptidases/metabolismo , Porphyromonas gingivalis/fisiologia , Processamento de Proteína Pós-Traducional , Aminoaciltransferases/química , Aminoaciltransferases/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Cisteína Endopeptidases/química , Cisteína Endopeptidases/genética , Endopeptidase K , Deleção de Genes , Peso Molecular , Mutação , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Mapeamento de Peptídeos , Porphyromonas gingivalis/enzimologia , Sinais Direcionadores de Proteínas , Estrutura Terciária de Proteína , Proteólise , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo
14.
Infect Immun ; 84(9): 2575-85, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27354442

RESUMO

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogen Porphyromonas gingivalis is the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened several Porphyromonas species isolated from companion animals-P. asaccharolytica, P. circumdentaria, P. endodontalis, P. levii, P. gulae, P. macacae, P. catoniae, and P. salivosa-for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that of Porphyromonas gingivalis Only P. gulae exhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in the P. gulae strain ATCC 51700 and all publicly available 12 draft genomes of P. gulae strains. P. gulae ATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those in P. gingivalis W50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytose P. gulae ATCC 51700 and the fimbriated P. gingivalis ATCC 33277 at similar levels. In response to P. gulae ATCC 51700, macrophages secreted higher levels of cytokines than those induced by P. gingivalis ATCC 33277 but lower than those induced by P. gingivalis W50, except for the interleukin-6 response. Our results indicate that P. gulae exhibits virulence characteristics similar to those of the human periodontal pathogen P. gingivalis and therefore may play a key role in the development of periodontitis in companion animals.


Assuntos
Periodontite/microbiologia , Porphyromonas gingivalis/imunologia , Porphyromonas gingivalis/patogenicidade , Porphyromonas/imunologia , Porphyromonas/patogenicidade , Fatores de Virulência/imunologia , Virulência/imunologia , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/microbiologia , Animais , Infecções por Bacteroidaceae/imunologia , Infecções por Bacteroidaceae/microbiologia , Linhagem Celular , Modelos Animais de Doenças , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Humanos , Interleucina-6/imunologia , Macrófagos/imunologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C
15.
PLoS Pathog ; 10(3): e1003955, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24603978

RESUMO

Porphyromonas gingivalis and Treponema denticola are strongly associated with chronic periodontitis. These bacteria have been co-localized in subgingival plaque and demonstrated to exhibit symbiosis in growth in vitro and synergistic virulence upon co-infection in animal models of disease. Here we show that during continuous co-culture a P. gingivalis:T. denticola cell ratio of 6∶1 was maintained with a respective increase of 54% and 30% in cell numbers when compared with mono-culture. Co-culture caused significant changes in global gene expression in both species with altered expression of 184 T. denticola and 134 P. gingivalis genes. P. gingivalis genes encoding a predicted thiamine biosynthesis pathway were up-regulated whilst genes involved in fatty acid biosynthesis were down-regulated. T. denticola genes encoding virulence factors including dentilisin and glycine catabolic pathways were significantly up-regulated during co-culture. Metabolic labeling using 13C-glycine showed that T. denticola rapidly metabolized this amino acid resulting in the production of acetate and lactate. P. gingivalis may be an important source of free glycine for T. denticola as mono-cultures of P. gingivalis and T. denticola were found to produce and consume free glycine, respectively; free glycine production by P. gingivalis was stimulated by T. denticola conditioned medium and glycine supplementation of T. denticola medium increased final cell density 1.7-fold. Collectively these data show P. gingivalis and T. denticola respond metabolically to the presence of each other with T. denticola displaying responses that help explain enhanced virulence of co-infections.


Assuntos
Porphyromonas gingivalis/metabolismo , Simbiose/fisiologia , Treponema denticola/metabolismo , Técnicas de Cocultura , Coinfecção , Microscopia Eletrônica de Varredura , Análise de Sequência com Séries de Oligonucleotídeos , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/crescimento & desenvolvimento , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma , Treponema denticola/genética , Treponema denticola/crescimento & desenvolvimento
16.
Microb Pathog ; 94: 60-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26541672

RESUMO

Chronic periodontitis has a polymicrobial biofilm aetiology. Polymicrobial biofilms are complex, dynamic microbial communities formed by two or more bacterial species that are important for the persistence and proliferation of participating microbes in the environment. Interspecies adherence, which often involves bacterial surface-associated molecules, and communications are essential in the spatial and temporal development of a polymicrobial biofilm, which in turn is necessary for the overall fitness of a well-organized multispecies biofilm community. In the oral cavity, interactions between key oral bacterial species, including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, are essential for the progression of chronic periodontitis. In vivo, P. gingivalis and T. denticola are frequently found to co-exist in deep periodontal pockets and have been co-localized to the superficial layers of subgingival plaque as microcolony blooms adjacent to the pocket epithelium, suggesting possible interbacterial interactions that contribute towards disease. The motility and chemotactic ability of T. denticola, although not considered as classic virulence factors, are likely to be important in the synergistic biofilm formation with P. gingivalis. In vitro, P. gingivalis and T. denticola display a symbiotic relationship in nutrient utilization and growth promotion. Together these data suggest there is an intimate relationship between these two species that has evolved to enhance their survival and virulence.


Assuntos
Placa Dentária/microbiologia , Gengiva/microbiologia , Porphyromonas gingivalis/fisiologia , Tannerella forsythia/crescimento & desenvolvimento , Treponema denticola/fisiologia , Adesinas Bacterianas/fisiologia , Biofilmes/crescimento & desenvolvimento , Quimiotaxia/fisiologia , Periodontite Crônica/microbiologia , Contagem de Colônia Microbiana , Humanos , Interações Microbianas , Bolsa Periodontal/microbiologia , Simbiose , Virulência
17.
Med Mycol ; 54(8): 856-64, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27354487

RESUMO

Oral biofilms comprise of extracellular polysaccharides and polymicrobial microorganisms. The objective of this study was to determine the effect of polymicrobial interactions of Candida albicans, Actinomyces naeslundii, and Streptococcus mutans on biofilm formation with the hypotheses that biofilm biomass and metabolic activity are both C. albicans strain and growth medium dependent. To study monospecific biofilms, C. albicans, A. naeslundii, and S. mutans were inoculated into artificial saliva medium (ASM) and RPMI-1640 in separate vials, whereas to study polymicrobial biofilm formation, the inoculum containing microorganisms was prepared in the same vial prior inoculation into a 96-well plate followed by 72 hours incubation. Finally, biofilm biomass and metabolic activity were measured using crystal violet and XTT assays, respectively. Our results showed variability of monospecies and polymicrobial biofilm biomass between C. albicans strains and growth medium. Based on cut-offs, out of 32, seven RPMI-grown biofilms had high biofilm biomass (HBB), whereas, in ASM-grown biofilms, 14 out of 32 were HBB. Of the 32 biofilms grown in RPMI-1640, 21 were high metabolic activity (HMA), whereas in ASM, there was no biofilm had HMA. Significant differences were observed between ASM and RPMI-grown biofilms with respect to metabolic activity (P <01). In conclusion, biofilm biomass and metabolic activity were both C. albicans strain and growth medium dependent.


Assuntos
Actinomyces/fisiologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Meios de Cultura/química , Interações Microbianas , Streptococcus mutans/fisiologia , Actinomyces/crescimento & desenvolvimento , Actinomyces/metabolismo , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Formazans/análise , Violeta Genciana/análise , Modelos Biológicos , Saliva/microbiologia , Coloração e Rotulagem , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/metabolismo
18.
Int J Paediatr Dent ; 26(3): 173-83, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25967851

RESUMO

BACKGROUND: Whilst the global burden of caries is increasing, the trajectory of decay in young children and the point at which prevention should occur has not been well established. AIM: To identify the 'natural history' of dental caries in early childhood. DESIGN: A birth cohort study was established with 467 mother/child dyads followed at 1, 6, 12, 18, and 36 months of age. Parent-completed surveys captured demographic, social, and behavioural data, and oral examinations provided clinical and data. RESULTS: Eight per cent of children (95% confidence interval (CI): 5-12%) at 18 months and 23% (95% CI: 18-28%) at 36 months experienced decay. Interesting lesion behaviour was found between 18 and 36 months, with rapid development of new lesions on sound teeth (70% of teeth, 95% CI: 63-76%) and regression of many lesions from non-cavitated lesions to sound (23% of teeth, 95% CI: 17-30%). Significant associations were found between soft drink consumption and lesion progression. CONCLUSIONS: Findings suggest optimal time periods for screening and prevention of a disease which significantly impacts multiple health and well-being outcomes across the life course.


Assuntos
Cárie Dentária/epidemiologia , Austrália/epidemiologia , Pré-Escolar , Estudos de Coortes , Cárie Dentária/prevenção & controle , Feminino , Humanos , Lactente , Masculino
19.
FEMS Yeast Res ; 15(5): fov038, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26054855

RESUMO

Microbial interactions are necessarily associated with the development of polymicrobial oral biofilms. The objective of this study was to determine the coaggregation of eight strains of Candida albicans with Actinomyces naeslundii and Streptococcus mutans. In autoaggregation assays, C. albicans strains were grown in RPMI-1640 and artificial saliva medium (ASM) whereas bacteria were grown in heart infusion broth. C. albicans, A. naeslundii and S. mutans were suspended to give 10(6), 10(7) and 10(8) cells mL(-1) respectively, in coaggregation buffer followed by a 1 h incubation. The absorbance difference at 620 nm (ΔAbs) between 0 h and 1 h was recorded. To study coaggregation, the same protocol was used, except combinations of microorganisms were incubated together. The mean ΔAbs% of autoaggregation of the majority of RPMI-1640-grown C. albicans was higher than in ASM grown. Coaggregation of C. albicans with A. naeslundii and/or S. mutans was variable among C. albicans strains. Scanning electron microscopy images showed that A. naeslundii and S. mutans coaggregated with C. albicans in dual- and triculture. In conclusion, the coaggregation of C. albicans, A. naeslundii and S. mutans is C. albicans strain dependent.


Assuntos
Actinomyces/fisiologia , Candida albicans/classificação , Candida albicans/fisiologia , Agregação Celular/fisiologia , Streptococcus mutans/fisiologia , Biofilmes/crescimento & desenvolvimento , Meios de Cultura , Microscopia Eletrônica de Varredura , Saliva Artificial
20.
Antimicrob Agents Chemother ; 58(1): 378-85, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24165189

RESUMO

Bacterial pathogens commonly associated with chronic periodontitis are the spirochete Treponema denticola and the Gram-negative, proteolytic species Porphyromonas gingivalis and Tannerella forsythia. These species rely on complex anaerobic respiration of amino acids, and the anthelmintic drug oxantel has been shown to inhibit fumarate reductase (Frd) activity in some pathogenic bacteria and inhibit P. gingivalis homotypic biofilm formation. Here, we demonstrate that oxantel inhibited P. gingivalis Frd activity with a 50% inhibitory concentration (IC50) of 2.2 µM and planktonic growth of T. forsythia with a MIC of 295 µM, but it had no effect on the growth of T. denticola. Oxantel treatment caused the downregulation of six P. gingivalis gene products and the upregulation of 22 gene products. All of these genes are part of a regulon controlled by heme availability. There was no large-scale change in the expression of genes encoding metabolic enzymes, indicating that P. gingivalis may be unable to overcome Frd inhibition. Oxantel disrupted the development of polymicrobial biofilms composed of P. gingivalis, T. forsythia, and T. denticola in a concentration-dependent manner. In these biofilms, all three species were inhibited to a similar degree, demonstrating the synergistic nature of biofilm formation by these species and the dependence of T. denticola on the other two species. In a murine alveolar bone loss model of periodontitis oxantel addition to the drinking water of P. gingivalis-infected mice reduced bone loss to the same level as the uninfected control.


Assuntos
Antinematódeos/farmacologia , Antinematódeos/uso terapêutico , Pirantel/análogos & derivados , Treponema denticola/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Camundongos , Periodontite/microbiologia , Porphyromonas gingivalis/efeitos dos fármacos , Pirantel/farmacologia , Pirantel/uso terapêutico , Succinato Desidrogenase/metabolismo , Treponema denticola/enzimologia
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