A5088785560- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Antibiotics Pharmacokinetics and Efficacy
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Cystic Fibrosis Research Advances
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Bacterial Identification and Susceptibility Testing
- Antimicrobial Peptides and Activities
- Biochemical and Molecular Research
- Carbohydrate Chemistry and Synthesis
- Biosensors and Analytical Detection
- Antifungal resistance and susceptibility
- Polymer Surface Interaction Studies
- Oral microbiology and periodontitis research
- Microbial Metabolism and Applications
- Microbial Community Ecology and Physiology
- Enzyme Catalysis and Immobilization
- Probiotics and Fermented Foods
- Antibiotic Use and Resistance
Christie (Canada)
2025
McGill University Health Centre
2010-2024
McGill University
2011-2023
Aegera Therapeutics (Canada)
2005
Queen's University
2003
McMaster University
1994-1997
University of Tennessee at Knoxville
1996
The University of Queensland
1974
Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought be a key mechanism producing tolerance. Here we show that the tolerance nutrient-limited and biofilm Pseudomonas aeruginosa mediated active responses starvation, rather than passive effects arrest. protective controlled starvation-signaling stringent response (SR), our experiments link SR-mediated reduced levels oxidant stress...
Slow-growing bacteria and biofilms are notoriously tolerant to antibiotics. Oritavancin is a lipoglycopeptide with multiple mechanisms of action that contribute its bactericidal against exponentially growing gram-positive pathogens, including the inhibition cell wall synthesis perturbation membrane barrier function. We sought determine whether oritavancin could eradicate cells known be many antimicrobial agents, is, stationary-phase biofilm cultures Staphylococcus aureus in vitro. exhibited...
Significance Antibiotic tolerance causes antibiotic treatment failure and promotes the emergence of genotypic resistance in chronic infections, such as those caused by pathogen Pseudomonas aeruginosa . Laboratory stationary-phase bacteria exhibit a slow growing metabolically quiescent state associated with high levels multidrug likely analogous to vivo environment during infection. We demonstrate that superoxide dismutases confer bacteria, identify link between (p)ppGpp-mediated stress...
Nanopillars have been shown to mechanically damage bacteria, suggesting a promising strategy for future antibacterial surfaces. However, the mechanisms underlying this phenomena remain unclear, which ultimately limits translational potential toward real-world applications. Using real-time and end-point analysis techniques, we demonstrate that in contrast initial expectations, bacteria on multiple hydrophilic "mechano-bactericidal" surfaces remained viable unless exposed moving air–liquid...
MexXY is an aminoglycoside-inducible multidrug transporter shown to contribute intrinsic and acquired aminoglycoside resistance in laboratory isolates of Pseudomonas aeruginosa. To assess its contribution 14 clinical demonstrating a panaminoglycoside phenotype unlikely be explained solely by modification, expression mexXY these was examined reverse transcription-PCR. Elevated levels were evident for most strains compared with those detected aminoglycoside-susceptible control strain, although...
Oritavancin, a lipoglycopeptide, possesses bactericidal activity against Gram-positive bacteria including vancomycin-resistant Staphylococcus aureus and enterococci. To understand the time dependence of oritavancin activity, we have undertaken time-kill experiments isolates S. aureus, Enterococcus faecalis faecium, recent antibiotic-resistant strains.Six strains [methicillin-susceptible (MSSA), methicillin-resistant (MRSA), vancomycin-intermediate (VISA), (VRSA)] five enterococci...
Oritavancin is an investigational lipoglycopeptide in clinical development for the treatment of acute bacterial skin and structure infections. In this study, we demonstrate that oritavancin causes membrane depolarization permeabilization leading to cell death Gram-positive pathogens these effects are attributable 4'-chlorobiphenylmethyl group molecule.
Oritavancin, a semisynthetic lipoglycopeptide with activity against gram-positive bacteria, has multiple mechanisms of action, including the inhibition cell wall synthesis and perturbation membrane potential. Approved guidelines for broth microdilution MIC assays dalbavancin, another lipoglycopeptide, require inclusion 0.002% polysorbate 80. To investigate potential impact 80 on oritavancin susceptibility assays, we quantified recovery [(14)C]oritavancin from assay plates without examined...
Nanopillar-textured surfaces are of growing interest because their ability to kill bacteria through physical damage without relying on antimicrobial chemicals. Although research antibacterial nanopillars has progressed significantly in recent years, the effect nanopillar hydrophobicity bactericidal activity remains elusive. In this study, we investigated mechano-bactericidal efficacy etched silicon against Pseudomonas aeruginosa at hydrophobicities from superhydrophilic superhydrophobic....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBroad Spectrum Aminoglycoside Phosphotransferase Type III from Enterococcus: Overexpression, Purification, and Substrate SpecificityG. A. McKay, P. R. Thompson, G. D. WrightCite this: Biochemistry 1994, 33, 22, 6936–6944Publication Date (Print):June 7, 1994Publication History Published online1 May 2002Published inissue 7 June 1994https://pubs.acs.org/doi/10.1021/bi00188a024https://doi.org/10.1021/bi00188a024research-articleACS PublicationsRequest...
Oritavancin is a semisynthetic lipoglycopeptide in clinical development for serious gram-positive infections. This study describes the synergistic activity of oritavancin combination with gentamicin, linezolid, moxifloxacin, or rifampin time-kill studies against methicillin-susceptible, vancomycin-intermediate, and vancomycin-resistant Staphylococcus aureus.
As a ubiquitous environmental organism and an important human pathogen, Pseudomonas aeruginosa readily adapts responds to wide range of conditions habitats. The intricate regulatory networks that link quorum sensing other global regulators allow P. coordinate its gene expression cell signaling in response different growth stressors. Upon nutrient transitions starvation, as well stresses, the stringent is activated, mediated by signal (p)ppGpp. produces family molecules called HAQ...
Cannabis sativa (marijuana) is used by millions of people around the world. C. produces hundreds secondary metabolites including cannabinoids, flavones and terpenes. Terpenes are a broad class organic compounds that give cannabis other plants its aroma. Previous studies have demonstrated terpenes may exert anti-inflammatory properties on immune cells. However, it not known whether derived from alone or in combination with cannabinoid ∆9-THC impacts function alveolar macrophages, specialized...
Bacterial resistance to the aminoglycoside antibiotics is manifested primarily through expression of enzymes which covalently modify these drugs. One important mechanism modification ATP-dependent O-phosphorylation, catalyzed by a family kinases. The structure one kinases, APH(3')-IIIa has recently been determined x-ray crystallography, and general fold strikingly similar eukaryotic protein kinases (Hon, W. C., McKay, G. A., Thompson, P. R., Sweet, R. M., Yang, D. S. Wright, D., Berghuis, A....
ABSTRACT A homologue of the algC gene, responsible for production a phosphoglucomutase (PGM) associated with LPS and alginate biosynthesis in Pseudomonas aeruginosa , spgM was cloned from Stenotrophomonas maltophilia . The gene shown to encode bifunctional enzyme both PGM phosphomannomutase activities. Mutants lacking produced less than SpgM + parent strain had tendency shorter O polysaccharide chains. No changes chemistry were obvious as result loss Significantly, however, mutants displayed...
Chronic Pseudomonas aeruginosa lung infections are associated with progressive epithelial damage and function decline. In addition to its role in tissue injury, the persistent presence of P. aeruginosa–secreted products may also affect repair ability, raising need for new antivirulence therapies. The purpose our study was better understand outcomes exoproducts exposure on airway processes identify a strategy counteract their deleterious effect. We found that significantly decreased wound...
Cyanophycin is a bacterial polymer mainly used for nitrogen storage. It composed of peptide backbone L-aspartate residues with L-arginines attached to their side chains through isopeptide bonds. degraded in two steps: Cyanophycinase cleaves the into β-Asp-Arg dipeptides, which are hydrolyzed free Asp and Arg by enzymes possessing isoaspartyl dipeptide hydrolase activity. Two unrelated this activity, dipeptidase (IadA) aminopeptidase (IaaA) have been shown degrade but bacteria encode...
Bacterial resistance to aminoglycoside-aminocyclitol antibiotics is mediated primarily by covalent modification of the drugs a variety enzymes. One such modifying enzyme, 3′-aminoglycoside phosphotransferase, which produced Gram-positive cocci as Enterococcus and Streptococcus inactivates broad range aminoglycosides ATP-dependent phosphorylation specific hydroxyl residues on antibiotics. Through use dead-end product inhibitor studies, we present first detailed examination kinetic mechanism...
The goal of this study was to isolate, screen, and characterize Arctic microbial isolates from Expedition Fjord, Axel Heiberg Island, Nunavut, Canada capable inhibiting the growth foodborne clinically relevant pathogens. bacteria were isolated twelve different high habitats pertaining active layer permafrost soil, saline spring sediments, lake endoliths. This achieved using (1) cryo-iPlate, an innovative in situ cultivation device within soil (2) bulk plating samples by undergraduate...
The airway mucosal microenvironment is crucial for host defense against inhaled pathogens but remains poorly understood. We report here that the surface normally undergoes surprisingly large excursions in pH during breathing can reach 9.0 inhalation, making it most alkaline fluid body. Transient alkalinization requires luminal bicarbonate and membrane-bound carbonic anhydrase 12 (CA12) antimicrobial. Luminal concentration CA12 expression are both reduced cystic fibrosis (CF), mucus...
Pseudomonas aeruginosa causes chronic airway infections, a major determinant of lung inflammation and damage in cystic fibrosis (CF). Loss-of-function lasR mutants commonly arise during CF are associated with accelerated function decline patients induce exaggerated neutrophilic model systems. In this study, we investigated how modulate epithelial membrane bound ICAM-1 (mICAM-1), surface adhesion molecule, determined its impact on vitro vivo. We demonstrated that LasR-deficient strains...