Silencing the nosocomial pathogen Serratia marcescens by glyceryl trinitrate

Background: Quorum sensing is a cell-to-cell communication system in bacteria that controls the production of virulence factors. Serratia marcescens is a causative agent of hospital-acquired infections that shows high resistance to antibiotics. This makes the treatment of these infections difficult. Quorum sensing regulates the production of virulence factors of S. marcescens such as prodigiosin, protease, swimming and swarming motilities and formation of biofilms. Inhibition of quorum sensing may be an alternative to antibiotic treatment to avoid emergence of resistance.Objectives: Testing the ability of glyceryl trinitrate to inhibit quorum sensing and virulence factors of Serratia marcescens.Methods: The inhibiting activities of sub-inhibitory concentration of glyceryl trinitrate against the quorum-sensing regulated violacein pigment in Chromobacterium violaceum CV026 was performed to evaluate the anti-quorum sensing effect of glyceryl trinitrate. The anti-virulence activity was assessed against prodigiosin, protease, biofilm formation in addition to swimming and swarming motilities.Results: Glyceryl trinitrate at at a concentration of 0.25 mg/ml produced significant inhibitory effects against violacein (67.01%), prodigiosin (82.67%), protease, swimming (36.72%) and swarming (79.31%) motilities and biofilm formation (87.83%).Conclusion: Glyceryl trinitrate is a quorum sensing and virulence inhibitor that may be useful in treatment of nosocomial infections caused by Serratia marcescens.Keywords: Serratia marcescens, quorum sensing, virulence, glyceryl trinitrate

Design of compact stop-band extended microstrip low-pass filters by employing mutual-coupled square-shaped defected ground structures

A new technique to reduce the size, improve the rejection in the stop-band of a low-pass filter using modified defected ground structure (DGS) is proposed. An equivalent circuit model is used to study the DGS characteristics. The parameters are extracted by using a simple circuit analysis method. Several comparisons between the EM-simulations and the circuit simulations of the new structure are demonstrated to show the validity of the proposed equivalent circuit model. We demonstrated that the filter can provide a sharp transition domain and a wide rejection in stop-band. To further verify the new technique, a filter employing the new deformed DGS is fabricated and measured. The agreement between the simulation and the measured results confirms the effectiveness of the proposed concept. © 2008 Wiley Periodicals, Inc. Microwave Opt Technol Lett 50: 1107–1111, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.23273Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58033/1/23273_ftp.pd

Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa

Background: Quorum sensing is a mechanism of intercellular communication that controls the production of virulence factors in Pseudomonas aeruginosa. Inhibition of quorum sensing can disarm the virulence factors without exerting stress on bacterial growth that leads to emergence of antibiotic resistance.Objectives: Finding a new quorum sensing inhibitor and determining its inhibitory activities against virulence factors of Pseudomonas aeruginosa PAO1 strain.Methods: Quorum sensing was evaluated by estimation of violacein production by Chromobacterium violaceum CV026. Molecular docking was used to investigate the possible binding of metformin to LasR and rhlR receptors. The inhibition of pyocyanin, hemolysin, protease, elastase in addition to swimming and twitching motilities, biofilm formation and resistance to oxidative stress by metformin was also assessed.Results: Metformin significantly reduced the production of violacein pigment. Significant inhibition of pyocyanin, hemolysin, protease and elastase was achieved. Metformin markedly decreased biofilm formation, swimming and twitching motilities and increased the sensitivity to oxidative stress. In the molecular docking study, metformin could bind to LasR by hydrogen bonding and electrostatic interaction and to rhlR by hydrogen bonding only.Conclusion: Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection.Keywords: Metformin, Pseudomonas aeruginosa, quorum sensing, virulence inhibitio

Silencing the nosocomial pathogen Serratia marcescens by glyceryl trinitrate

Background: Quorum sensing is a cell-to-cell communication system in bacteria that controls the production of virulence factors. Serratia marcescens is a causative agent of hospital-acquired infections that shows high resistance to antibiotics. This makes the treatment of these infections difficult. Quorum sensing regulates the production of virulence factors of S. marcescens such as prodigiosin, protease, swimming and swarming motilities and formation of biofilms. Inhibition of quorum sensing may be an alternative to antibiotic treatment to avoid emergence of resistance. Objectives: Testing the ability of glyceryl trinitrate to inhibit quorum sensing and virulence factors of Serratia marcescens. Methods: The inhibiting activities of sub-inhibitory concentration of glyceryl trinitrate against the quorum-sensing regulated violacein pigment in Chromobacterium violaceum CV026 was performed to evaluate the anti-quorum sensing effect of glyceryl trinitrate. The anti-virulence activity was assessed against prodigiosin, protease, biofilm formation in addition to swimming and swarming motilities. Results: Glyceryl trinitrate at at a concentration of 0.25 mg/ml produced significant inhibitory effects against violacein (67.01%), prodigiosin (82.67%), protease, swimming (36.72%) and swarming (79.31%) motilities and biofilm formation (87.83%). Conclusion: Glyceryl trinitrate is a quorum sensing and virulence inhibitor that may be useful in treatment of nosocomial infections caused by Serratia marcescens

Effect of SPIO Nanoparticle Concentrations on Temperature Changes for Hyperthermia via MRI

Magnetic nanoparticles (MNPs) are being developed for a wide range of biomedical applications. In particular, hyperthermia involves heating the MNPs through exposure to an alternating magnetic field (AMF). These materials offer the potential for selectively by heating cancer tissue locally and at the cellular level. This may be a successful method if there are enough particles in a tumor possessing sufficiently high specific absorption rate (SAR) to deposit heat quickly while minimizing thermal damage to surrounding tissue. The current research aim is to study the influence of super paramagnetic iron oxides Fe3O4 (SPIO) NPs concentration on the total heat energy dose and the rate of temperature change in AMF to induce hyperthermia in Ehrlich carcinoma cells implanted in female mice. The results demonstrated a linearly increasing trend between these two factors

Glyceryl trinitrate blocks staphyloxanthin and biofilm formation in Staphylococcus aureus

Background: Staphylococcus aureus is an important nosocomial bacterium that is responsible for a number of infections that may be fatal. The treatment of such infections is limited by emergence of antibiotic resistance. Targeting virulence of Staphylococcus aureus may provide an alternative option to antibiotic that may bypass the emergence of resistant strains due to lack of stress on viability. Objectives: Investigation of the ability of glyceryl trinitrate (GTN) to inhibit staphyloxanthin, biofilm and tolerance to oxidative stress. Methods: The disk sensitivity method was used to detect the methicillin resistance of Staphylococcus aureus. The effect of sub-inhibitory concentration of GTN on biofilm formation, staphyloxanthin production and tolerance to oxidative stress was evaluated. Molecular docking study was used to investigate the ability of GTN to bind to dehydrosqualene synthase enzyme. Results: GTN showed a significant inhibition of biofilm, staphyloxanthin and tolerance to oxidative stress. In the molecular docking study, it was found that GTN could bind to dehydrosqualene synthase enzyme by hydrogen bonding,electrostatic interaction and pi-cation interaction. Conclusion: The present study revealed the ability of GTN to serve as a potential anti-virulence candidate for attenuation of S. aureus pathogenicity. DOI: https://dx.doi.org/10.4314/ahs.v19i1.10 Cite as: Abbas HA, Elsherbini AM, MA S. Glyceryl trinitrate blocks staphyloxanthin and biofilm formation in Staphylococcus aureus. Afri Health Sci. 2019;19(1). 1376-1384. https://dx.doi.org/10.4314/ahs.v19i1.1

Repurposing metformin as a quorum sensing inhibitor in Pseudomonas aeruginosa

Background: Quorum sensing is a mechanism of intercellular communication that controls the production of virulence factors in Pseudomonas aeruginosa. Inhibition of quorum sensing can disarm the virulence factors without exerting stress on bacterial growth that leads to emergence of antibiotic resistance. Objectives: Finding a new quorum sensing inhibitor and determining its inhibitory activities against virulence factors of Pseudomonas aeruginosa PAO1 strain. Methods: Quorum sensing was evaluated by estimation of violacein production by Chromobacterium violaceum CV026. Molecular docking was used to investigate the possible binding of metformin to LasR and rhlR receptors. The inhibition of pyocyanin, hemolysin, protease, elastase in addition to swimming and twitching motilities, biofilm formation and resistance to oxidative stress by metformin was also assessed. Results: Metformin significantly reduced the production of violacein pigment. Significant inhibition of pyocyanin, hemolysin, protease and elastase was achieved. Metformin markedly decreased biofilm formation, swimming and twitching motilities and increased the sensitivity to oxidative stress. In the molecular docking study, metformin could bind to LasR by hydrogen bonding and electrostatic interaction and to rhlR by hydrogen bonding only. Conclusion: Metformin can act as a quorum sensing inhibitor and virulence inhibiting agent that may be useful in the treatment of Pseudomonas aeruginosa infection

Association of Aβ with Ceramide-Enriched Astrosomes Mediates Aβ Neurotoxicity

Amyloid-β (Aβ) associates with extracellular vesicles termed exosomes. It is not clear whether and how exosomes modulate Aβ neurotoxicity in Alzheimer\u27s disease (AD). We show here that brain tissue and serum from the transgenic mouse model of familial AD (5xFAD) and serum from AD patients contains ceramide-enriched and astrocyte-derived exosomes (termed astrosomes) that are associated with Aβ. In Neuro-2a cells, primary cultured neurons, and human induced pluripotent stem cell-derived neurons, Aβ-associated astrosomes from 5xFAD mice and AD patient serum were specifically transported to mitochondria, induced mitochondrial clustering, and upregulated the fission protein Drp-1 at a concentration corresponding to 5 femtomoles Aβ/L of medium. Aβ-associated astrosomes, but not wild type or control human serum exosomes, mediated binding of Aβ to voltage-dependent anion channel 1 (VDAC1) and subsequently, activated caspases. Aβ-associated astrosomes induced neurite fragmentation and neuronal cell death, suggesting that association with astrosomes substantially enhances Aβ neurotoxicity in AD and may comprise a novel target for therapy