In Silico Novel Drug Design Targeting the Oral Microbiome: Endodontic and Periodontal Pathogenic Bacteria

Understanding plant–microbe interactions is crucial for improving plants’ productivity and protection. Constraint-based metabolic modeling is one of the possible ways to investigate the bacterial adaptation to different ecological niches and may give insights into the metabolic versatility of plant pathogenic bacteria. We reconstructed a raw metabolic model of the emerging plant pathogenic bacterium Pectobacterium parmentieri SCC3193 with the use of KBase. The model was curated by using inParanoind and phenotypic data generated with the use of the OmniLog system. Metabolic modeling was performed through COBRApy Toolbox v. 0.10.1. The curated metabolic model of P. parmentieri SCC3193 is highly reliable, as in silico obtained results overlapped up to 91% with experimental data on carbon utilization phenotypes. By mean of flux balance analysis (FBA), we predicted the metabolic adaptation of P. parmentieri SCC3193 to two different ecological niches, relevant for the persistence and plant colonization by this bacterium: soil and the rhizosphere. We performed in silico gene deletions to predict the set of essential core genes for this bacterium to grow in such environments. We anticipate that our metabolic model will be a valuable element for defining a set of metabolic targets to control infection and spreading of this plant pathogen.

Download Full-text

Impact of the Diet on the Formation of Oxidative Stress and Inflammation Induced by Bacterial Biofilm in the Oral Cavity

Materials ◽

10.3390/ma14061372 ◽

2021 ◽

Vol 14 (6) ◽

pp. 1372

Author(s):

Ilona Rowińska ◽

Adrianna Szyperska-Ślaska ◽

Piotr Zariczny ◽

Robert Pasławski ◽

Karol Kramkowski ◽

...

Keyword(s):

Oxidative Stress ◽

Oral Cavity ◽

Pathogenic Bacteria ◽

Soft Tissues ◽

Bacterial Flora ◽

Bacterial Biofilm ◽

Oral Microbiome ◽

Diffusion Method ◽

Oral Diseases ◽

Periodontal Tissues

The diet is related to the diversity of bacteria in the oral cavity, and the less diverse microbiota of the oral cavity may favor the growth of pathogenic bacteria of all bacterial complexes. Literature data indicate that disturbances in the balance of the bacterial flora of the oral cavity seem to contribute to both oral diseases, including periodontitis, and systemic diseases. If left untreated, periodontitis can damage the gums and alveolar bones. Improper modern eating habits have an impact on the oral microbiome and the gut microbiome, which increase the risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease and cancer. The subject of our consideration is the influence of the traditional diet on the formation of oxidative stress and inflammation caused by bacterial biofilm in the oral cavity. Through dental, biomedical and laboratory studies, we wanted to investigate the effect of individual nutrients contained in specific diets on the induction of oxidative stress inducing inflammation of the soft tissues in the oral cavity in the presence of residual supra- and subgingival biofilm. In our research we used different types of diets marked as W, T, B, F and noninvasively collected biological material in the form of bacterial inoculum from volunteers. The analyzed material was grown on complete and selective media against specific strains of all bacterial complexes. Additionally, the zones of growth inhibition were analyzed based on the disc diffusion method. The research was supplemented with dental and periodontological indicators. The research was supplemented by the application of molecular biology methods related to bacterial DNA isolation, PCR reactions and sequencing. Such selected methods constitute an ideal screening test for the analysis of oral bacterial microbiota. The obtained results suggest that certain types of diet can be an effective prophylaxis in the treatment of civilization diseases such as inflammation of the oral cavity along with periodontal tissues and gingival pockets.

Download Full-text

Drug Design of GLP-1 Receptor Agonists: Importance of In silico Methods

Current Pharmaceutical Design ◽

10.2174/1381612826666201118094502 ◽

2020 ◽

Vol 26 ◽

Author(s):

Smriti Sharma ◽

Vinayak Bhatia

Keyword(s):

Drug Design ◽

In Silico ◽

Experimental Studies ◽

Receptor Agonists ◽

Drug Molecules ◽

Glucagon Like Peptide 1 ◽

Long Acting ◽

Almost All ◽

Available Information ◽

Novel Drug

: Drug design based on degradation-resistant, long-acting Glucagon-like peptide-1 receptor (GLP-1R) agonists for treating type 2 diabetes is attracting lot of attention. Here, the authors have examined in detail how in silico drug design is aiding in developing novel GLP-1 receptor agonist drugs. Their pharmacotherapy and adverse effects have also been summarized. After the analysis of currently available information on this topic, the authors feel that in silico method is a great auxiliary tool in almost all the experimental studies on GLP-1 receptors and is highly efficient in identifying novel drug molecules that can act as GLP-1 receptor agonists.

Download Full-text

Assessment of Oral Microbiome Changes in Healthy and COVID-19-Affected Pregnant Women: A Narrative Review

Microorganisms ◽

10.3390/microorganisms9112385 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2385

Author(s):

Andrea Butera ◽

Carolina Maiorani ◽

Annalaura Morandini ◽

Manuela Simonini ◽

Arianna Colnaghi ◽

...

Keyword(s):

Oral Cavity ◽

Periodontal Disease ◽

Pregnant Women ◽

Pathogenic Bacteria ◽

Circulatory System ◽

Fusobacterium Nucleatum ◽

Membrane Receptors ◽

Oral Microbiome ◽

Gingival Diseases ◽

Bidirectional Interactions

During pregnancy, there are several metabolic changes and an alteration in the composition of microorganisms that inhabit the oral cavity, with an increase in pathogenic bacteria that promote the onset of gingival diseases. This review is based on research in reference to the PICO model (Problem/Intervention/Comparison/Outcome), related to changes in the oral microbiome of pregnant women and possible oral consequences in patients with COVID-19. The results showed a growth of some pathogenic bacteria in pregnant women, including Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, and the selective growth of the Prevotella intermedia, Porphyromonas gingivalis and Tannerella species, probably due to the fact that these bacteria use progesterone as a source of nutrition. These same bacteria are implicated in the development of periodontal disease. Periodontal pockets have bidirectional interactions between the oral cavity and the systemic circulatory system through the peripheral gingival blood vessels. The affinity of the SARS-CoV-2 virus to specific membrane receptors is now clear, and could involve the internal and external epithelial lining or the fibroblasts of the periodontal ligament. According to the results of the present review, the control of oral microbiome changes during pregnancy would be welcomed. The use of probiotics could help clinicians manage pregnant patients, reducing inflammatory indexes. Future studies should focus not only on changes in the level of the oral microbiome in pregnancy or the correlation between periodontal disease and COVID-19, but also on oral changes induced by both clinical situations.

Download Full-text

The role of probiotics in correction of microbiocenosis and cytokine balance of the oral cavity of patient with chronic inflammatory disease of periodont

Periodontology ◽

10.33925/1683-3759-2020-25-4-323-330 ◽

2020 ◽

Vol 25 (4) ◽

pp. 323-330

Author(s):

E. S. Ovcharenko ◽

V. V. Erichev ◽

S. I. Risovannij ◽

T. V. Aksenova ◽

S. V. Melekhov ◽

...

Keyword(s):

Oral Cavity ◽

Periodontal Diseases ◽

Treatment Protocol ◽

Chronic Inflammatory Disease ◽

Oral Microbiome ◽

Comprehensive Treatment ◽

Local Immunity ◽

Treatment Techniques ◽

Before And After

Relevance. A long-term inflammation in the oral cavity, unreasonable treatment of periodontal patients with antibiotics cause imbalance between certain types of fungal-bacterial associations accompanied by oral dysbiosis and change of local immune status. So, development and application of new comprehensive diagnosis and treatment techniques in periodontal patients, use of products for correction of microbiota and local immunity are a current and a long-term task. Purpose is to optimize the comprehensive treatment protocol of inflammatory periodontal diseases by introducing probiotics and evaluation of oral microbiome and cytokine profile.Materials and methods. 140 patients were examined. Of these 60 patients had chronic generalized plaque-induced gingivitis and 60 patients suffered from moderate chronic generalized periodontitis. Bacterial and fungal microbiome was assessed and the host immune response was evaluated in all patients before and after the treatment. Half of the patients were treated conventionally and the other half were treated according to a modified scheme: probiotic “Bifidumbacterin Forte” was added.Results. A large number of yeast-like fungi Candida and commensal bacteria were detected in periodontal pockets of patients with chronic generalized plaque-induced gingivitis and moderate chronic generalized periodontitis. That correlates with a significant increase of pro-inflammatory cytokines (TNF-α, IL—8), decrease of concentration of INF-γ and increase of antiinflammatory cytokine IL-4.Conclusion. Changes in clinical, microbiological and immunological values during a modified combination therapy with a probiotic and during a conventional treatment demonstrated that effectiveness of treatment of chronic gingivitis and chronic periodontitis increased by 40% and 37% respectively.

Download Full-text

Periodontopathogens: a new view. Systematic review. Part 2

Стоматология детского возраста и профилактика ◽

10.33925/1683-3031-2020-20-2-160-167 ◽

2020 ◽

Vol 20 (2) ◽

pp. 160-167

Author(s):

E. S. Slazhneva ◽

E. A. Tikhomirova ◽

V. G. Atrushkevich

Keyword(s):

Systematic Review ◽

Periodontal Disease ◽

Pathogenic Bacteria ◽

Periodontal Diseases ◽

Oral Microbiome ◽

Controlled Trials ◽

New Paradigm ◽

Microbial Composition ◽

Randomized Controlled ◽

The Past

Relevance. The modern view of periodontitis as a dysbiotic disease that occurs as a result of changes in the microbial composition of the subgingival region is considered in a systematic review.Purpose. To study a new paradigm of development of generalized periodontitis.Materials and methods. Randomized controlled trials (RCTS) were selected for the study, including cluster RCTS, controlled (non-randomized) microbiological and clinical studies of the oral microbiome in adult patients with generalized periodontitis over the past 10 years.Results. The transition from a symbiotic microflora to a dysbiotic pathogenic community triggers the host's inflammatory response, which contributes to the development of periodontal diseases. Modern ideas about periodontal pathogenic bacteria dictate new requirements for the treatment of periodontal diseases. The second part of the review examines the microbial profiles of periodontal disease in various nosological forms, the mechanisms of the immune response and approaches to the treatment of periodontal disease from the perspective of biofilm infection.Conclusions. As follows from modern literature periodontitis is to a certain extent caused by the transition from a harmonious symbiotic bacterial community to a dysbiotic one. Recent scientific studies have shown that not single microorganism is not able to cause disease but the microbial community as a whole leads to the development of pathology.

Download Full-text

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

Current Pharmaceutical Design ◽

10.2174/1381612826666200928161721 ◽

2020 ◽

Vol 26 ◽

Author(s):

Smriti Sharma ◽

Vinayak Bhatia

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Drug Design ◽

In Silico ◽

Drug Targets ◽

Development Process ◽

Phytochemical Analysis ◽

Computational Drug Design ◽

Novel Drugs ◽

Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

Download Full-text

Appraisal of the role of In silico Methods in Pyrazole based drug design

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200901184146 ◽

2020 ◽

Vol 20 ◽

Author(s):

Smriti Sharma ◽

Vinayak Bhatia

Keyword(s):

Drug Design ◽

In Silico ◽

Md Simulations ◽

Quantitative Structure Activity Relationship ◽

Field Analysis ◽

Computational Techniques ◽

Neuroprotective Drugs ◽

Pharmacological Potential ◽

Available Information ◽

Anti Fungal

: Pyrazole and its derivatives are a pharmacologically significant active scaffold that have innumerable physiological and pharmacological activities. They can be very good targets for the discovery of novel anti-bacterial, anticancer, anti-inflammatory, anti-fungal, anti-tubercular, antiviral, antioxidant, antidepressant, anti-convulsant and neuroprotective drugs. This review focuses on the importance of in silico manipulations of pyrazole and its derivatives for medicinal chemistry. The authors have discussed currently available information on the use of computational techniques like molecular docking, structure-based virtual screening (SBVS), molecular dynamics (MD) simulations, quantitative structure activity relationship (QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to drug design using pyrazole moieties. Pyrazole based drug design is mainly dependent on the integration of experimental and computational approaches. The authors feel that more studies need to be done to fully explore the pharmacological potential of the pyrazole moiety and in silico method can be of great help.

Download Full-text

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190121105851 ◽

2019 ◽

Vol 18 (31) ◽

pp. 2731-2740 ◽

Cited By ~ 3

Author(s):

Sandeep Tiwari ◽

Debmalya Barh ◽

M. Imchen ◽

Eswar Rao ◽

Ranjith K. Kumavath ◽

...

Keyword(s):

Broad Spectrum ◽

In Silico ◽

Pathogenic Bacteria ◽

In Vitro Study ◽

Docking Studies ◽

Acetate Kinase ◽

E Coli ◽

Pathogenic Escherichia Coli ◽

Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Download Full-text