Photoswitch dissociation from a G protein-coupled receptor resolved by time-resolved serial crystallography.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors in humans. The binding and dissociation of ligands tunes the inherent conformational flexibility of these important drug targets towards distinct functional states. Here we show how to trigger and resolve protein-ligand interaction dynamics within the human adenosine A receptor.

A multi-reservoir extruder for time-resolved serial protein crystallography and compound screening at X-ray free-electron lasers.

Serial crystallography at X-ray free-electron lasers (XFELs) permits the determination of radiation-damage free static as well as time-resolved protein structures at room temperature. Efficient sample delivery is a key factor for such experiments. Here, we describe a multi-reservoir, high viscosity extruder as a step towards automation of sample delivery at XFELs.

Watching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography.

The binding and release of ligands from their protein targets is central to fundamental biological processes as well as to drug discovery. Photopharmacology introduces chemical triggers that allow the changing of ligand affinities and thus biological activity by light. Insight into the molecular mechanisms of photopharmacology is largely missing because the relevant transitions during the light-triggered reaction cannot be resolved by conventional structural biology.

Statins and oral biofilm: Simvastatin as a promising drug to control periodontal dysbiosis.

Objectives: This study evaluated antimicrobial activity of atorvastatin, pravastatin, rosuvastatin, and simvastatin against oral bacteria, and the interaction of simvastatin with standard antimicrobials (amoxicillin and metronidazole).

Methods: Minimal inhibitory concentration assays were performed with Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Actinomyces odontolyticus, Streptococcus oralis, Streptococcus mitis, Streptococcus salivarius, Streptococcus sanguinis, and Streptococcus gordonii; checkerboard microdilution assays between simvastatin and standard antimicrobials; monospecies and multispecies biofilms.

Results: Simvastatin showed the best antimicrobial activity against most species (MIC range from 3.

Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1.

Lysosomes coordinate cellular metabolism and growth upon sensing of essential nutrients, including cholesterol. Through bioinformatic analysis of lysosomal proteomes, we identified lysosomal cholesterol signaling (LYCHOS, previously annotated as G protein-coupled receptor 155), a multidomain transmembrane protein that enables cholesterol-dependent activation of the master growth regulator, the protein kinase mechanistic target of rapamycin complex 1 (mTORC1). Cholesterol bound to the amino-terminal permease-like region of LYCHOS, and mutating this site impaired mTORC1 activation.

Correction: Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.

[This corrects the article DOI: 10.1371/journal.pone.

Quantification and gene expression of group species associated with dentinal lesions in early childhood caries.

Background: Considering that the group is strongly associated with caries progression, the use of lactobacilli as probiotics must be balanced due to their possible involvement in dental caries.

Objective: This study aimed to detect and quantify , and group species in the active and arrested dentinal lesions of preschoolers. It also aimed to determine the expression profiles of lactobacilli genes related to adhesion, extracellular polymeric substance regulation, and pyruvate oxidation.

Glass-ionomer cement modifies the gene expression of Streptococcus mutans providing a lower virulent biofilm.

Purpose: To evaluate the effect of glass-ionomer cement (GIC) on gene expression (gtfC, gtfD, covR, and vicR) of Streptococcus mutans (S. mutans) biofilms at 2, 4 and 24 hours.

Methods: Six groups were tested according to the materials and time observation, as follows: ceramic (IPS Empress Esthetic), as the control group, and GIC (Ketac Molar Easymix); and time points of S.

Physical-Mechanical Properties of Bulk Fill Composites Submitted to Biodegradation by Streptococcus mutans.

The aim of this study was to evaluate the Streptococcus mutans biofilm influence on the roughness (Ra), gloss (GU), surface hardness (KHN) and flexural strength (FS) of high viscosity bulk fill composites. Filtek Bulk Fill (FBF), Tetric N Ceram Bulk Fill (TNC), X-tra fil Bulk Fill (XF) and Filtek Z350 (FZ) were used. Ten discs of each composite were prepared for Ra, KHN and GU and 20 bars for the FS.

Addition of hydrogen peroxide to methylene blue conjugated to β-cyclodextrin in photodynamic antimicrobial chemotherapy in S. mutans biofilm.

Objective: This study evaluated the effect of hydrogen peroxide addition on β-cyclodextrin-conjugated methylene blue in antimicrobial photodynamic therapy(a-PDT) in S. mutans biofilm model using laser or light emitting diode (LED) (λ = 660 nm).

Methods: A preliminary assay was performed to evaluate the cytotoxicity of hydrogen peroxide in oral fibroblasts by the colorimetric method (MTT).

Effect of iodonium salt and chitosan on the physical and antibacterial properties of experimental infiltrants.

Resinous infiltrants are indicated in the treatment of incipient carious lesions, and further development of these materials may contribute to greater control of these lesions. The aim of this study was to analyze the physical and antibacterial properties of experimental infiltrants containing iodonium salt and chitosan. Nine experimental infiltrants were formulated by varying the concentration of the diphenyliodonium salt (DPI) at 0, 0.

Trans,trans-farnesol, an antimicrobial natural compound, improves glass ionomer cement properties.

A series of experiments were conducted to characterize a novel restorative material. We explored the effect on biological, physical and chemical properties of glass ionomer cement (GIC) adding-the naturally occurring tt-farnesol (900 mM). Two groups were accomplished for all assays: GIC+tt-farnesol and GIC (control).

Combined Effectiveness of β-Cyclodextrin Nanoparticles in Photodynamic Antimicrobial Chemotherapy on Oral Biofilms.

This study aimed to investigate if β-cyclodextrin nanoparticles potentiate the photodynamic antimicrobial chemotherapy (PACT) effects in single and microcosm oral biofilms using methylene blue (MB) and a red laser. Studies of PACT have demonstrated promising effects; however, the association of nanoparticles with photosensitizers could enhance the antimicrobial result. Biofilms were grown on enamel blocks either with or in a microcosm model (salivary microorganisms) supplemented with sucrose.

Oral streptococci show diversity in resistance to complement immunity.

Purpose: Mechanisms underlying systemic infections by oral species of Mitis (Streptococcus mitis, Streptococcus oralis) and Sanguinis (Streptococcus gordonii, Streptococcus sanguinis) commensal streptococci are poorly understood. This study investigates profiles of susceptibility to complement-mediated host immunity in representative strains of these four species, which were isolated from oral sites or from the bloodstream.

Methodology: Deposition of complement opsonins (C3b/iC3b), and surface binding to C-reactive protein (CRP) and to IgG antibodies were quantified by flow cytometry in 34 strains treated with human serum (HS), and compared to rates of opsonophagocytosis by human PMN mediated by complement (CR1/3) and/or IgG Fc (FcγRII/III) receptors.

Quantitative analysis of biofilm bacteria according to different stages of early childhood caries.

Objective: Monitoring selected key species related to health or disease may facilitate caries risk assessment and discovery of novel ecological preventive and therapeutic approaches. This study aimed at quantifying Actinomyces naeslundii, Bifidobacterium spp., Lactobacillus acidophilus, Lactobacillus casei group, Streptococcus gordonii, Mitis group and Streptococcus mutans by quantitative polymerase chain reaction (qPCR) in dental biofilm from Brazilian children with different stages of early childhood caries (ECC).

Activity of Streptococcus mutans VicR Is Modulated by Antisense RNA.

The VicRK 2-component system of Streptococcus mutans regulates genes associated with cell wall biogenesis and biofilm formation. A putative RNase III-encoding gene ( rnc) is located downstream from the vicRKX operon. The goals of this study were to investigate the potential role of VicR in the regulation of adjacent downstream genes and evaluate transcription levels of vicR during planktonic and biofilm growth.

Treatment of periodontitis in smokers with multiple sessions of antimicrobial photodynamic therapy or systemic antibiotics: A randomized clinical trial.

Background: The aim of this study was to evaluate the effects of non-surgical periodontal therapies on smokers with chronic periodontitis, involving multiple adjunctive applications of antimicrobial photodynamic therapy (aPDT), and systemic metronidazole (MTZ) with amoxicillin (AMX).

Methods: All participants were treated with scaling and root planing (SRP). Seventeen patients received 400 mg of MTZ and 500 mg of AMX three times per day for 7 days (MTZ + AMX).

A novel Triclosan Methacrylate-based composite reduces the virulence of Streptococcus mutans biofilm.

The use of antimicrobial monomers, linked to the polymer chain of resin composites, is an interesting approach to circumvent the effects of bacteria on the dental and material surfaces. In addition, it can likely reduce the incidence of recurrent caries lesions. The aim of this study was to evaluate the effects of a novel Triclosan Methacrylate (TM) monomer, which was developed and incorporated into an experimental resin composite, on Streptococcus mutans (S.

Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation.

is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, SptRS (SptRS ), affecting survival in saliva and biofilm formation. Isogenic mutants of (SKsptR) and (SKsptS) showed reduced cell counts in assays of viability in saliva compared to those of parent strain SK36 and complemented mutants.

Viability and Osteogenic Differentiation of Human Periodontal Ligament Progenitor Cells Are Maintained After Incubation With Porphyromonas gingivalis Protein Extract.

Background: Porphyromonas gingivalis (Pg) is a major periodontal pathogen that contains immunostimulatory components. Periodontal ligament mesenchymal stem cells (PDLMSCs) are responsible for regeneration of the periodontium that is lost due to periodontitis. Pathologic factors within the microenvironment that impair resident PDLMSCs are not well understood.

The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity.

Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRK of S. mutans regulates the synthesis of and interaction with sucrose-derived exopolysaccharides (EPS), processes associated with oral and systemic virulence.

Oral cavities of healthy infants harbour high proportions of Streptococcus salivarius strains with phenotypic and genotypic resistance to multiple classes of antibiotics.

Emerging antibiotic resistance in the oropharyngeal microbiota, of which Streptococcus salivarius is a prominent species, represents a challenge for treating paediatric populations. In this study, we investigated the role of Streptococcussalivarius as a reservoir for antibiotic resistance genes (ARG) in the oral microbiota by analysing 95 Streptococcussalivarius isolates from 22 healthy infants (2-16 months of age). MICs of penicillin G, amoxicillin, erythromycin, tetracycline, doxycycline and streptomycin were determined.

Molecular detection of bacteria associated to caries activity in dentinal lesions.

Objectives: This study aimed at identifying and quantifying Actinomyces naeslundii, Bifidobacterium spp., Streptococcus mitis group, Lactobacillus acidophilus, Lactobacillus casei group, Streptococcus gordonii, and Streptococcus mutans in active and inactive carious dentine lesions of children with early childhood caries by using quantitative polymerase chain reaction.

Material And Methods: Fifty-six dentin lesion samples, classified as active (n = 39) or inactive (n = 17), were collected from children aged from 2 to 5 years old.

CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood.

Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovR) modulates susceptibility to complement opsonization and survival in blood.

Insights into the Virulence Traits of Streptococcus mutans in Dentine Carious Lesions of Children with Early Childhood Caries.

Streptococcus mutans is an oral bacterium considered to play a major role in the development of dental caries. This study aimed to investigate the prevalence of S. mutans in active and arrested dentine carious lesions of children with early childhood caries and to examine the expression profile of selected S.