scholarly journals Relevance of Topographic Parameters on the Adhesion and Proliferation of Human Gingival Fibroblasts and Oral Bacterial Strains

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Miguel Ángel Pacha-Olivenza ◽  
Ricardo Tejero ◽  
María Coronada Fernández-Calderón ◽  
Eduardo Anitua ◽  
María Troya ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Strong Acid ◽  
Human Saliva ◽  
Gingival Fibroblast ◽  
Bacterial Strains ◽  
Implant Surface ◽  
General Improvement ◽  
Oral Implant ◽  
Prosthetic Component ◽  
Cell Adhesion And Proliferation

Dental implantology allows replacement of failing teeth providing the patient with a general improvement of health. Unfortunately not all reconstructions succeed, as a consequence of the development of infections of bacterial origin on the implant surface. Surface topography is known to modulate a differential response to bacterial and mammalian cells but topographical measurements are often limited to vertical parameters. In this work we have extended the topographical measurements also to lateral and hybrid parameters of the five most representative implant and prosthetic component surfaces and correlated the results with bacterial and mammalian cell adhesion and proliferation outcomes. Primary human oral gingival fibroblast (gum cells) and the bacterial strains: Streptococcus mutans, Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans, implicated in infectious processes in the oral/implant environment were employed in the presence or absence of human saliva. The results confirm that even though not all the measured surface is available for bacteria to adhere, the overall race for the surface between cells and bacteria is more favourable to the smoother surfaces (nitrided, as machined or lightly acid etched) than to the rougher ones (strong acid etched or sandblasted/acid etched).

scholarly journals Imaging Sensitive and Drug-Resistant Bacterial Infection with [11C]-TMP: In Vitro and First-in-Human Evaluation

2021 ◽  
Author(s):  
Iris K Lee ◽  
Daniel A Jacome ◽  
Joshua K Cho ◽  
Vincent Tu ◽  
Anthony Young ◽  
...  
Keyword(s):  
Bacterial Infection ◽  
Mammalian Cells ◽  
Bacterial Infections ◽  
The Body ◽  
Response Monitoring ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Critical Question ◽  
In Vitro Uptake

Recently, several molecular imaging strategies have developed to image bacterial infections in humans. Nuclear approaches, specifically positron emission tomography (PET), affords sensitive detection and the ability to non-invasively locate infections deep within the body. Two key radiotracer classes have arisen: metabolic approaches targeting bacterial specific biochemical transformations, and antibiotic-based approaches that have inherent selectivity for bacteria over mammalian cells. A critical question for clinical application of antibiotic radiotracers is whether resistance to the template antibiotic abrogates specific uptake, thus diminishing the predictive value of the diagnostic test. We recently developed small-molecule PET radiotracers based on the antibiotic trimethoprim (TMP), including [11C]-TMP, and have shown their selectivity for imaging bacteria in preclinical models. Here, we measure the in vitro uptake of [11C]-TMP in pathogenic susceptible and drug-resistant bacterial strains. Both resistant and susceptible bacteria showed similar in vitro uptake, which led us to perform whole genome sequencing of these isolates to identify the mechanisms of TMP resistance that permit retained radiotracer binding. By interrogating these isolate genomes and a broad panel of previously sequenced strains, we reveal mechanisms where uptake or binding of TMP radiotracers can potentially be maintained despite the annotation of genes conferring antimicrobial resistance. Finally, we present several examples of patients with both TMP-sensitive and drug-resistant infections in our first-in-human experience with [11C]-TMP. This work underscores the ability of an antibiotic radiotracer to image bacterial infection in patients, which may allow insights into human bacterial pathogenesis, infection diagnosis, and antimicrobial response monitoring.

scholarly journals Drug resistant gut bacteria mimic a host mechanism for anticancer drug clearance

2019 ◽  
Author(s):  
Peter Spanogiannopoulos ◽  
Patrick H. Bradley ◽  
Jonathan Melamed ◽  
Ysabella Noelle Amora Malig ◽  
Kathy N. Lam ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Drug Disposition ◽  
Transcriptional Profiling ◽  
Drug Efficacy ◽  
Drug Clearance ◽  
Gut Bacteria ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Bacterial Strains

Microbiome surveys indicate that pharmaceuticals are the top predictor of inter-individual variations in gut microbial community structure1, consistent with in vitro evidence that non-antibiotic (i.e. host-targeted) drugs inhibit gut bacterial growth2and are subject to extensive metabolism by the gut microbiome3,4. In oncology, bacterial metabolism has been implicated in both drug efficacy5,6and toxicity7,8; however, the degree to which bacterial sensitivity and metabolism can be driven by conserved pathways also found in mammalian cells remains poorly understood. Here, we show that anticancer fluoropyrimidine drugs broadly inhibit the growth of diverse gut bacterial strains. Media supplementation, transcriptional profiling (RNA-seq), and bacterial genetics implicated pyrimidine metabolism as a key target in bacteria, as in mammalian cells. Drug resistant bacteria metabolized 5FU to its inactive metabolite dihydrofluorouracil (DHFU) mimicking the major host pathway for drug clearance. Functional orthologs of the bacterial operon responsible (preTA) are widespread across human gut bacteria from the Firmicutes and Proteobacteria phyla. The observed conservation of both the targets and pathways for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug disposition9, efficacy, and side effect profiles.

scholarly journals Physics Comes to the Aid of Medicine—Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 969
Author(s):  
Mateusz Cieśluk ◽  
Piotr Deptuła ◽  
Ewelina Piktel ◽  
Krzysztof Fiedoruk ◽  
Łukasz Suprewicz ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antimicrobial Agents ◽  
Antimicrobial Treatment ◽  
Point Of View ◽  
Diagnostic Methods ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Force Microscopy ◽  
Atomic Force ◽  
Recent Developments

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.

scholarly journals Antimicrobial Effects of Three Different Treatment Modalities on Dental Implant Surfaces

2017 ◽  
Vol 43 (6) ◽  
pp. 429-436 ◽  
Author(s):  
Olav I. Larsen ◽  
Morten Enersen ◽  
Anne Karin Kristoffersen ◽  
Ann Wennerberg ◽  
Dagmar F. Bunæs ◽  
...  
Keyword(s):  
Dental Implants ◽  
Dental Implant ◽  
Er:Yag Laser ◽  
Antimicrobial Effect ◽  
Positive Control ◽  
Treatment Modalities ◽  
Bacterial Strains ◽  
Implant Surface ◽  
Antimicrobial Effects ◽  
Dental Implant Surface

Resolution of peri-implant inflammation and re-osseointegration of peri-implantitis affected dental implants seem to be dependent on bacterial decontamination. The aims of the study were to evaluate the antimicrobial effects of 3 different instrumentations on a micro-textured dental implant surface contaminated with an avirulent or a virulent Porphyromonas gingivalis strain and to determine alterations to the implant surface following instrumentation. Forty-five dental implants (Straumann SLA) were allocated to 3 treatment groups: Er:YAG laser, chitosan brush, and titanium curette (10 implants each) and a positive (10 implants) and a negative (5 implants) control. Each treatment group and the positive control were split into subgroups of 5 implants subsequently contaminated with either the avirulent or virulent P. gingivalis strain. The antimicrobial effect of instrumentation was evaluated using checkerboard DNA–DNA hybridization. Implant surface alterations were determined using a light interferometer. Instrumentation significantly reduced the number of attached P. gingivalis (P < .001) with no significant differences among groups (P = .310). A significant overall higher median score was found for virulent compared with avirulent P. gingivalis strains (P = .007); the Er:YAG laser uniquely effective removing both bacterial strains. The titanium curette significantly altered the implant surface micro-texture. Neither the Er:YAG laser nor the chitosan brush significantly altered the implant surface. The 3 instrumentations appear to have a similar potential to remove P. gingivalis. The titanium curette significantly altered the microstructure of the implant surface.

scholarly journals Bacteria facilitate viral co-infection of mammalian cells and promote genetic recombination

2017 ◽  
Author(s):  
A.K. Erickson ◽  
P.R. Jesudhasan ◽  
M.J. Mayer ◽  
A. Narbad ◽  
S.E. Winter ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Genetic Recombination ◽  
Enteric Viruses ◽  
Intestinal Bacteria ◽  
Enteric Virus ◽  
Viral Fitness ◽  
Host Cells ◽  
Bacterial Strains ◽  
Viral Recombination ◽  
Viral Genomes

SUMMARYIntestinal bacteria promote infection of several mammalian enteric viruses, but the mechanisms and consequences are unclear. We screened a panel of 41 bacterial strains as a platform to determine how different bacteria impact enteric viruses. We found that most bacterial strains bound poliovirus, a model enteric virus. Given that each bacterium bound multiple virions, we hypothesized that bacteria may deliver multiple viral genomes to a mammalian cell even when very few virions are present, such as during the first replication cycle after inter-host transmission. We found that exposure to certain bacterial strains increased viral co-infection even when the ratio of virus to host cells was low. Bacteria-mediated viral co-infection correlated with bacterial adherence to cells. Importantly, bacterial strains that induced viral co-infection facilitated viral fitness restoration through genetic recombination. Thus, bacteria-virus interactions may increase viral fitness through viral recombination at initial sites of infection, potentially limiting abortive infections.

scholarly journals Synthesis, Antifungal Activity, and Biocompatibility of Novel 1,4-Diazabicyclo[2.2.2]Octane (DABCO) Compounds and DABCO-Containing Denture Base Resins

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Jenny L. Herman ◽  
Yapin Wang ◽  
Elizabeth A. Lilly ◽  
Thomas E. Lallier ◽  
Brian M. Peters ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Fungicidal Activity ◽  
Fungal Growth ◽  
Cell Types ◽  
Aliphatic Chain ◽  
Gingival Fibroblast ◽  
Denture Base ◽  
Content Type ◽  
Denture Stomatitis ◽  
Oral Infections

ABSTRACT The fungal pathogen Candida albicans causes a variety of oral infections, including denture stomatitis, which is characterized by inflammation of the oral mucosa in direct contact with dentures and affects a significant number of otherwise healthy denture wearers. While antifungal treatment reduces symptoms, infections are often recurrent. One strategy to address this problem is to incorporate compounds with fungicidal activities into denture materials to prevent colonization. Our laboratory synthesized novel derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO), which is an organic compound typically used as a catalyst in polymerization reactions. DABCO derivatives with different aliphatic chain lengths (DC16, DC16F, DC18, and C6DC16), as well as methacrylate monomers conjugated to DABCO compounds (DC11MAF and C2DC11MAF), were synthesized and tested for antimicrobial activity. All the compounds exhibited fungicidal activity against several Candida species at concentrations ranging between 2 and 4 μg/ml. Moreover, acrylic denture base resins fabricated to contain 1, 2, or 4 wt% DABCO compounds inhibited surface C. albicans biofilm formation, as well as fungal growth, in disc diffusion assays. Remarkably, discs (4 wt%) aged for 2 months also exhibited approximately 100% growth-inhibitory activity. While some DABCO compounds exerted intermediate to high cytotoxicity against mammalian oral cell types, DC11MAF and denture base resin discs containing 2 or 4 wt% C2DC11MAF exhibited relatively low cytotoxicity against periodontal ligament (PDL) cell and gingival fibroblast (GF) lines, as well as primary oral epithelial cells. These studies demonstrate that DABCO derivatives can be incorporated into denture materials and exert fungicidal activity with minimal cytotoxicity to mammalian cells. DC11MAF and C2DC11MAF are considered strong candidates as therapeutic or preventive alternatives against Candida-associated denture stomatitis.

Bismuth(III) Thiophosphinates: Understanding How a Small Atomic Change Influences Antibacterial Activity and Mammalian Cell Viability

2020 ◽  
Vol 73 (12) ◽  
pp. 1226
Author(s):  
Dimuthu C. Senevirathna ◽  
Rebekah N. Duffin ◽  
Liam J. Stephens ◽  
Megan E. Herdman ◽  
Melissa V. Werrett ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Cell Viability ◽  
Mammalian Cell ◽  
Mammalian Cells ◽  
Bacterial Strains ◽  
X Ray Diffraction ◽  
Gram Negative ◽  
X Ray ◽  
X Ray Crystallography ◽  
Biological Studies

Diphenylphosphinothioic acid (HSP(=O)Ph2) and diphenylphosphinodithioic acid (HSP(=S)Ph2) have been used to synthesise four BiIII complexes: 1 [Bi(SP(=O)Ph2)3], 2 [BiPh(SP(=O)Ph2)2], 3 [BiPh2(SP(=O)Ph2)], and 4 [Bi(SP(=S)Ph2)3], using BiPh3 and [Bi(OtBu)3] as bismuth sources. The complexes have been characterised by NMR spectroscopy, mass spectrometry, infrared spectroscopy, powder X-ray diffraction, and singe crystal X-ray crystallography (2–4). Biological studies indicated that despite complexes 2 and 3 reducing mammalian cell viability, their antibacterial activity provides a good degree of selectivity towards both Gram positive and Gram negative bacterial strains. The minimum inhibitory concentrations for complexes 2 and 3 are in the range of 0.52–5.5µM towards the bacteria tested. Homoleptic complexes 1 and 4 were generally less active towards both bacterial and mammalian cells.

Differences in stability profiles and thermodynamics of inhibitor binding to target protein purified from E. coli, mammalian cells, and human saliva

2014 ◽  
Vol 185 ◽  
pp. S109
Author(s):  
Justina Kazokaite ◽  
Goda Milinaviciute ◽  
Joana Smirnoviene ◽  
Virginija Dudutiene ◽  
Alexey Smirnov ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Human Saliva ◽  
Target Protein ◽  
Inhibitor Binding ◽  
E Coli

scholarly journals The Analysis of Bifenox and Dichlobenil Toxicity in Selected Microorganisms and Human Cancer Cells

2019 ◽  
Vol 16 (21) ◽  
pp. 4137 ◽  
Author(s):  
Agata Jabłońska-Trypuć ◽  
Urszula Wydro ◽  
Lluis Serra-Majem ◽  
Elżbieta Wołejko ◽  
Andrzej Butarewicz
Keyword(s):  
Oxidative Stress ◽  
Mammalian Cells ◽  
Human Cancer ◽  
Environmental Pollutants ◽  
Cellular Level ◽  
Human Organism ◽  
Bacterial Strains ◽  
Human Cancer Cells ◽  
Oxidative Stress Parameters ◽  
Stress Parameters

Bifenox and Dichlobenil belong to the commonly used in Poland in agriculture group of herbicides and their residues are often detected in the environment. They are poorly known regarding their possible carcinogenic and antibacterial effect at the cellular level. Therefore, we decided to study their activity in bacterial strains Aliivibrio fisheri, E. coli, P. aeruginosa, and C. albicans (yeast) and human cancer ZR-75-1 cells. Compounds under study exhibit stimulatory effect on analyzed bacterial strains. The study performed on mammalian cells better reflects the influence of environmental pollutants on human organism, therefore we evaluated the effect of herbicides on ZR-75-1 cells. Cells viability, apoptosis and selected oxidative stress parameters in ZR-75-1 cells were investigated. Both analyzed substances exhibit stimulatory effects on analyzed parameters, however they do not stimulate apoptosis which correlate positively with the induction of oxidative stress. Bifenox and Dichlobenil enhance oxidative stress parameters by the generation of high levels of ROS, which can lead to their adaptation and resistance to the standard treatment regimen.

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