Hemin availability induces coordinated DNA methylation and gene expression changes in .

Periodontal disease is a chronic inflammatory disease in which the oral pathogen plays an important role. expresses virulence determinants in response to higher hemin concentrations, but the underlying regulatory processes remain unclear. Bacterial DNA methylation has the potential to fulfil this mechanistic role.

Optimization of conditions for modeling of subgingival normobiosis and dysbiosis.

Modeling subgingival microbiome in health and disease is key to identifying the drivers of dysbiosis and to studying microbiome modulation. Here, we optimize growth conditions of our previously described subgingival microbiome model. Subgingival plaque samples from healthy and periodontitis subjects were used as inocula to grow normobiotic and dysbiotic microbiomes in MBEC assay plates.

Understanding dental caries as a non-communicable disease.

The recent developments in the science underpinning our knowledge of both the initiation of dental caries and the subsequent behaviour of lesions over time gives us a solid base to understand caries differently. Advances in understanding the human and oral microbiome have come in parallel with the recognition of the importance of balancing protective and pathological risk factors. Caries prevention and management is now about controlling risk factors to maintain a balanced intraoral biofilm ecology that guards against a continuing low pH driven by the frequent consumption of sugars.

Characterization of the Infant Immune System and the Influence and Immunogenicity of BCG Vaccination in Infant and Adult Rhesus Macaques.

In many countries where tuberculosis (TB) is endemic, the Bacillus Calmette-Guérin (BCG) vaccine is given as close to birth as possible to protect infants and children from severe forms of TB. However, BCG has variable efficacy and is not as effective against adult pulmonary TB. At present, most animal models used to study novel TB vaccine candidates rely on the use of adult animals.

Immunomodulatory streptococci that inhibit CXCL8 secretion and NFκB activation are common members of the oral microbiota.

Oral tissues are generally homeostatic despite exposure to many potential inflammatory agents including the resident microbiota. This requires the balancing of inflammation by regulatory mechanisms and/or anti-inflammatory commensal bacteria. Thus, the levels of anti-inflammatory commensal bacteria in resident populations may be critical in maintaining this homeostatic balance.

A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen.

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis.

Applications of the oral microbiome in personalized dentistry.

Objective: In the era of personalized medicine, it is imperative that oral health is integrated into this concept. The oral cavity fosters a highly individualized microbiome that has evolved to promote oral health, and which exists in a dynamic balance with the host. Microecological changes to the biology of the mouth [e.

Enrichment of periodontal pathogens from the biofilms of healthy adults.

Periodontitis is associated with shifts in the balance of the subgingival microbiome. Many species that predominate in disease have not been isolated from healthy sites, raising questions as to the origin of these putative pathogens. The study aim was to determine whether periodontal pathogens could be enriched from pooled saliva, plaque and tongue samples from dentally-healthy adult volunteers using growth media that simulate nutritional aspects of the inflamed subgingival environment.

Differences in monocyte: lymphocyte ratio and Tuberculosis disease progression in genetically distinct populations of macaques.

Monocyte:lymphocyte ratio (M:L) has been identified as a risk factor in development of TB disease in children and those undergoing treatment for HIV in co-infected individuals. Retrospective analysis was performed using M:L data collected from TB modelling studies performed in Rhesus macaques of Indian genotype (RM), cynomolgus macaque of Chinese genotype (CCM) and cynomolgus macaque of Mauritian genotype (MCM), which found that the more susceptible populations (RM and MCM) had higher M:L ratios than the least susceptible population (CCM). Following Mycobacterium tuberculosis exposure, significant increases in M:L ratio were observed in susceptible RM and MCM within 12 weeks of TB infection, whereas M:L in CCM remained stable, suggesting that changes in M:L ratio may also act as a biomarker of TB disease progression.

Root Surface Biofilms and Caries.

Following gingival recession, which increases with age, the root surface becomes exposed, creating new environments for microbial colonization and biofilm formation. The formation of root surface biofilms is influenced by the availability and composition of saliva and gingival crevicular fluid; they provide components for the conditioning film (acquired root surface pellicle) and also act as a source of nutrients. The early bacterial colonizers of the root surface are similar to those found on the enamel, and Gram-positive species such as Streptococcus sanguinis, S.

Ecological Therapeutic Opportunities for Oral Diseases.

The three main oral diseases of humans, that is, caries, periodontal diseases, and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review, we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes.

Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the Joint EFP/ORCA workshop on the boundaries between caries and periodontal disease.

Background And Aims: The scope of this working group was to review (1) ecological interactions at the dental biofilm in health and disease, (2) the role of microbial communities in the pathogenesis of periodontitis and caries, and (3) the innate host response in caries and periodontal diseases.

Results And Conclusions: A health-associated biofilm includes genera such as Neisseria, Streptococcus, Actinomyces, Veillonella and Granulicatella. Microorganisms associated with both caries and periodontal diseases are metabolically highly specialized and organized as multispecies microbial biofilms.

The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity?

Background: Pyrazinamide (PZA) plays an essential part in the shortened six-month tuberculosis (TB) treatment course due to its activity against slow-growing and non-replicating organisms. We tested whether PZA preferentially targets slow growing cells of Mycobacterium tuberculosis that could be representative of bacteria that remain after the initial kill with isoniazid (INH), by observing the response of either slow growing or fast growing bacilli to differing concentrations of PZA.

Methods: M.

A Flow Cytometry Method for Rapidly Assessing Mycobacterium tuberculosis Responses to Antibiotics with Different Modes of Action.

Current methods for assessing the drug susceptibility of Mycobacterium tuberculosis are lengthy and do not capture information about viable organisms that are not immediately culturable under standard laboratory conditions as a result of antibiotic exposure. We have developed a rapid dual-fluorescence flow cytometry method using markers for cell viability and death. We show that the fluorescent marker calcein violet with an acetoxy-methyl ester group (CV-AM) can differentiate between populations of M.

Influence of saliva on the oral microbiota.

Saliva plays a major role in determining the composition and activity of the oral microbiota, via a variety of mechanisms. Molecules, mainly from saliva, form a conditioning film on oral surfaces, thus providing receptors for bacterial attachment. The attached cells use saliva components, such as glycoproteins, as their main source of nutrients for growth.

The commensal microbiota and the development of human disease - an introduction.

Humans have co-evolved with microorganisms, and both exist in a symbiotic or mutualistic relationship. We are colonised by a diverse, resident microbiota, which develop into structurally and functionally organised biofilms. The resident microorganisms gain a secure, warm, nutritious habitat from the host and, in return, contribute to the development of many important host functions.

Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315.

An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity.

Modulation of host responses by oral commensal bacteria.

Immunomodulatory commensal bacteria are proposed to be essential for maintaining healthy tissues, having multiple roles including priming immune responses to ensure rapid and efficient defences against pathogens. The default state of oral tissues, like the gut, is one of inflammation which may be balanced by regulatory mechanisms and the activities of anti-inflammatory resident bacteria that modulate Toll-like receptor (TLR) signalling or NF-κB activation, or influence the development and activities of immune cells. However, the widespread ability of normal resident organisms to suppress inflammation could impose an unsustainable burden on the immune system and compromise responses to pathogens.

Prospects of oral disease control in the future - an opinion.

The mouth supports a diverse microbiota which provides major benefits to the host. On occasions, this symbiotic relationship breaks down (dysbiosis), and disease can be a consequence. We argue that progress in the control of oral diseases will depend on a paradigm shift away from approaches that have proved successful in medicine for many diseases with a specific microbial aetiology.

Non-replicating Mycobacterium tuberculosis elicits a reduced infectivity profile with corresponding modifications to the cell wall and extracellular matrix.

A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M.