A5054273186- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Antibiotic Resistance in Bacteria
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Probiotics and Fermented Foods
- Escherichia coli research studies
- Lipid Membrane Structure and Behavior
- Bacterial Infections and Vaccines
- Cystic Fibrosis Research Advances
- Microbial Community Ecology and Physiology
- Glycosylation and Glycoproteins Research
- Antimicrobial agents and applications
- Salmonella and Campylobacter epidemiology
- Enzyme Structure and Function
- Vibrio bacteria research studies
- Gut microbiota and health
- Neonatal Respiratory Health Research
- Protist diversity and phylogeny
- Antimicrobial Peptides and Activities
- Cancer-related Molecular Pathways
- Viral gastroenteritis research and epidemiology
- Clostridium difficile and Clostridium perfringens research
- Cancer, Hypoxia, and Metabolism
University of Guelph
2016-2025
Agriculture and Agri-Food Canada
2021
National Institutes of Health
2007-2011
National Cancer Institute
2007-2010
Center for Cancer Research
2007-2010
McGill University
2004-2006
Brookhaven National Laboratory
2006
Toronto Metropolitan University
2001
The cytoplasmic membrane protein TonB spans the periplasm of Gram-negative bacterial cell envelope, contacts cognate outer receptors, and facilitates siderophore transport. receptor FhuA from Escherichia coli mediates TonB-dependent import ferrichrome. We report 3.3 angstrom resolution crystal structure carboxyl-terminal domain in complex with FhuA. stabilize FhuA's amino-terminal residues, including those consensus Ton box sequence that form an interprotein beta sheet through strand...
Signal transduction in bacterial chemotaxis is initiated by the binding of extracellular ligands to a specialized family methyl-accepting chemoreceptor proteins. Chemoreceptors cluster at distinct regions cell and form stable ternary complexes with histidine autokinase CheA adapter protein CheW. Here we report direct visualization spatial organization arrays intact Escherichia coli cells using cryo-electron tomography biochemical techniques. In wild-type cells, are arranged as an extended...
Pathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due part to inherent architecture biofilm community. The protection provided by limits dispersion and penetration reduces efficacy antibiotics that normally inhibit planktonic cell growth. Thus, alternative strategies are required combat persistent infections. properties silver have been known for decades, but silver-containing compounds recently...
Pseudomonas aeruginosa is a common opportunistic human pathogen known for its ability to adapt changes in environment during the course of infection. These adaptations include expression cell surface lipopolysaccharide (LPS), biofilm development, and production protective extracellular exopolysaccharide matrix. Outer membrane vesicles (OMVs) have been identified as an important component matrix P. biofilms are thought contribute development fitness these bacterial communities. The goal this...
Chronic polymicrobial lung infections are the chief complication in patients with cystic fibrosis. The dominant pathogen late-stage disease is Pseudomonas aeruginosa, which forms recalcitrant, structured communities known as biofilms. Many aspects of biofilm biology poorly understood; consequently, effective treatment these limited, and fibrosis remains fatal. Here we combined in-solution protein digestion triplicate growth-matched samples a high-performance mass spectrometry platform to...
ABSTRACT Increasing antibiotic resistance among pathogenic bacterial species is a serious public health problem and has prompted research examining the antibacterial effects of alternative compounds novel treatment strategies. Compounding this ability many bacteria to form biofilms during chronic infections. Importantly, these communities are often recalcitrant treatments that show effectiveness against acute infection. The antimicrobial properties silver have been known for decades, but...
Peptidoglycan hydrolases, or autolysins, play a critical role in cell wall remodeling and degradation, facilitating bacterial growth, division, separation. In Staphylococcus aureus, the so-called "major" autolysin, Atl, has long been associated with host adhesion; however, molecular basis underlying this phenomenon remains understudied. To investigate, we used type V glycopeptide antibiotic complestatin, which binds to peptidoglycan blocks activity of as chemical probe autolysin function. We...
Bacterial chemoreceptors undergo conformational changes in response to variations the concentration of extracellular ligands. These chemoreceptor structure initiate a series signaling events that ultimately result regulation rotation flagellar motor. Here we have used cryo-electron tomography combined with 3D averaging determine situ assemblies Escherichia coli cells been engineered overproduce serine Tsr. We demonstrate are organized as trimers receptor dimers and display two distinct...
Chemoreceptor arrays are macromolecular complexes that form extended assemblies primarily at the poles of bacterial cells and mediate chemotaxis signal transduction, ultimately controlling cellular motility. We have used cryo-electron tomography to determine spatial distribution molecular architecture signaling molecules comprise chemoreceptor in wild-type Caulobacter crescentus cells. demonstrate chemoreceptors organized as trimers receptor dimers, forming partially ordered hexagonally...
Antibiotic resistance constitutes one of the most serious threats to global public health and urgently requires new effective solutions. Bacteriophages are bacterial viruses increasingly recognized as being good alternatives traditional antibiotic therapies. In this study, efficacy phages, targeting different cell receptors, against Pseudomonas aeruginosa PAO1 biofilm planktonic cultures was evaluated over course 48 h. Although significant reductions in number viable cells were achieved for...
ABSTRACT Cystic fibrosis (CF) is caused by mutations in the CFTR gene and associated with progressive ultimately fatal infectious lung disease. There can be considerable variability disease severity among individuals same mutations, recent genome-wide association studies have identified secondary genetic factors that contribute to this. One of these modifier genes SLC6A14 , which encodes an amino acid transporter. Importantly, variants this been age at first acquisition Pseudomonas...
A recent workshop titled "Developing Models to Study Polymicrobial Infections," sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored development of new models study polymicrobial infections associated with airways persons cystic fibrosis (CF). The gathered 35+ investigators over two virtual sessions. Here, we present findings this workshop, summarize some challenges involved developing such models, and suggest three frameworks tackle complex problem. proposed here, believe,...
Abstract Non-Typhoidal Salmonella (NTS) is one of the most common food-borne pathogens worldwide, with poultry products being major vehicle for pathogenesis in humans. The use bacteriophage (phage) cocktails has recently emerged as a novel approach to enhancing food safety. Here, multireceptor phage cocktail five phages was developed and characterized. targets four receptors: O-antigen, BtuB, OmpC, rough strains. Structural analysis indicated that all belong unique families or subfamilies....
It is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target respiration with inhibitors oxidative phosphorylation highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed bulk and metabolic phenotype murine HER2-driven mammary tumors...
It is now recognized that mitochondria play a crucial role in tumorigenesis, however, it has become clear tumor metabolism varies significantly between cancer types. The failure of recent clinical trials attempting to directly target respiration with inhibitors oxidative phosphorylation highlighted the critical need for additional studies comprehensively assessing mitochondrial bioenergetics. Therefore, we systematically assessed bulk and metabolic phenotype murine HER2-driven mammary tumors...
The transition of the opportunistic pathogen Pseudomonas aeruginosa from free-living bacteria into surface-associated biofilm communities represents a viable target for prevention and treatment chronic infectious disease. We have established proteomics platform that identified 2443 1142 high-confidence proteins in P. whole cells outer-membrane vesicles (OMVs), respectively, at three time points during development (ProteomeXchange identifier PXD002605). analysis cellular systems, specifically...
Microbial biofilms are particularly resistant to antimicrobial therapies. These surface-attached communities protected against host defenses and pharmacotherapy by a self-produced matrix that surrounds fortifies them. Recent proteomic evidence also suggests some bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, undergo modifications within biofilm make them uniquely compared their planktonic (free-living) counterparts. This study examines 50 proteins in resistance...
Our understanding of the biofilm matrix components utilized by Gram-positive bacteria, and signalling pathways that regulate their production are largely unknown. In a companion study, we developed computational pipeline for unbiased identification homologous bacterial operons applied this algorithm to analysis synthase-dependent exopolysaccharide biosynthetic systems. Here, explore finding many species bacteria have with similarity Pseudomonas aeruginosa pel locus. characterization...
Pseudomonas aeruginosa is an opportunistic human pathogen and a leading cause of chronic infection in the lungs individuals with cystic fibrosis. After colonization, P. often undergoes phenotypic conversion to mucoidy, characterized by overproduction alginate exopolysaccharide. This correlated poorer patient prognoses. The majority genes required for synthesis, including lyase, algL, are located single operon. Previous investigations AlgL have resulted several divergent hypotheses regarding...