33 research outputs found
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
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
A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin’s physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach
Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.
PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks