A5029788409- Antibiotic Resistance in Bacteria
- Cystic Fibrosis Research Advances
- Vibrio bacteria research studies
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- Plant Pathogenic Bacteria Studies
- Metabolomics and Mass Spectrometry Studies
- Bacteriophages and microbial interactions
- Bioinformatics and Genomic Networks
- Bacterial Genetics and Biotechnology
- Legume Nitrogen Fixing Symbiosis
- Innovation and Socioeconomic Development
- Extracellular vesicles in disease
- Burkholderia infections and melioidosis
- Bacterial biofilms and quorum sensing
- Protein Structure and Dynamics
- Redox biology and oxidative stress
- Plant-Microbe Interactions and Immunity
- Antibiotics Pharmacokinetics and Efficacy
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Bee Products Chemical Analysis
- Machine Learning in Materials Science
- Innovative Microfluidic and Catalytic Techniques Innovation
- vaccines and immunoinformatics approaches
University of Manitoba
2017-2024
Memorial University of Newfoundland
2015-2017
Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology pathogenesis. Members of genus Burkholderia have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack suitable genetic edit GC-rich genomes has hampered exploration useful capacities and understanding pathogenic features. To address this, we developed CRISPR interference (CRISPRi) technology gene silencing...
To streamline the elucidation of antibacterial compounds’ mechanism action, comprehensive high-throughput assays interrogating multiple putative targets are necessary. However, current chemogenomic approaches for antibiotic target identification have not fully utilized multiplexing potential next-generation sequencing.
Screening for novel antibacterial compounds in small molecule libraries has a low success rate. We applied machine learning (ML)-based virtual screening activity and evaluated its predictive power by experimental validation. first binarized 29,537 according to their growth inhibitory (hit rate 0.87%) against the antibiotic-resistant bacterium Burkholderia cenocepacia described molecular features with directed-message passing neural network (D-MPNN). Then, we used data train an ML model that...
Abstract The cell envelope of Gram-negative bacteria belonging to the Burkholderia cepacia complex (Bcc) presents unique restrictions antibiotic penetration. As a consequence, Bcc species are notorious for causing recalcitrant multidrug-resistant infections in immunocompromised individuals. Here, we present results genome-wide screen envelope-associated resistance and susceptibility determinants cenocepacia clinical isolate. For this purpose, construct high-density, randomly-barcoded...
ABSTRACT Genome editing in non-model bacteria is important to understand gene-to-function links that may differ from those of model microorganisms. Although species the Burkholderia cepacia complex (Bcc) have great biotechnological capacities, limited genetic tools available and mitigate their pathogenic potential hamper utilization industrial applications. To broaden for Bcc species, we developed RhaCAST, a targeted DNA insertion platform based on CRISPR-associated transposase driven by...
Summary The glycophosphatidylinositol‐anchored cell surface receptor CD 24 (also called heat‐stable antigen) promotes the apoptosis of progenitor and precursor B‐lymphocytes. However, immediate proximal events that occur after engagement in B cells are not precisely understood. Using a bioinformatics analysis mouse ( Mus musculus ) gene expression data from Immunological Genome Project, we found known vesicle trafficking cellular organization genes have similar patterns to during B‐cell...
Chemical-genetic interaction profiling is a genetic approach that quantifies the susceptibility of set mutants depleted in specific gene product(s) to chemical compounds. With recent advances artificial intelligence, chemical-genetic profiles (CGIPs) can be leveraged predict mechanism action This achieved by using machine learning, where data from CGIP fed into learning platform along with descriptors develop chemogenetically trained model. As small molecules considered non-structural data,...
Drug repurposing efforts led to the discovery of bactericidal activity in auranofin, a gold-containing drug used treat rheumatoid arthritis. Auranofin kills Gram-positive bacteria by inhibiting thioredoxin reductase, an enzyme that scavenges reactive oxygen species (ROS). Despite presence reductase Gram-negative bacteria, auranofin is not always active against them. It clear whether lack several due cell envelope barrier or other ROS protective enzymes such as glutathione (GOR). We...
Abstract The CD24 cell surface receptor promotes apoptosis in developing B cells, and we recently found that it induces cells to release plasma membrane-derived, CD24-bearing microvesicles (MVs). Here have performed a systematic characterization of MVs released from WEHI-231 lymphoma response stimulation. We constitutively approximately 120 nm, an increase phosphatidylserine-positive MV release. RNA cargo is predominantly comprised 5S rRNA, regardless stimulation; however, causes decrease...
A diverse genetic toolkit is critical for understanding bacterial physiology and genotype-phenotype relationships. Inducible promoter systems are an integral part of this toolkit. In Burkholderia related species, the l-rhamnose-inducible among first choices due to its tight control lack viable alternatives. To improve upon maximum activity dynamic range, we explored effect system modifications in cenocepacia with a LacZ-based reporter. By combining bacteriophage T7 gene 10 stem-loop...
Antibiotic activity is limited by the physical construction of Gram-negative cell envelope. Species
Bacteria of the genus Burkholderia include pathogenic mallei, pseudomallei and cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment infections difficult. Bcc affects individuals with cystic fibrosis (CF) species B. cenocepacia is associated one worst clinical outcomes. Following repurposing auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized analogs activity Gram-negatives. In this work, show that two...
Bacteria of the Burkholderia cepacia complex (Bcc) are associated with significant decline lung functions in cystic fibrosis patients. Bcc infections virtually impossible to eradicate due their irresponsiveness antibiotics. The 2-thiocyanatopyridine derivative 11026103 is a novel, synthetic compound active against cenocepacia. To characterize mechanisms resistance 11026103, B. cenocepacia was subjected chemical mutagenesis, followed by whole genome sequencing. Parallel mutations resistant...
Glucose is the universal energy source and a critical substrate for lipid synthesis in mammalian cells. Analysis of both glucose cells important understanding regulation many cell types, but especially adipocytes, major storage fat mammals. The fluorescent 7-nitrobenz-2-oxa-1,3-diazole (NBD) derivative glucose, 2-NBDG, used to monitor uptake lipid-selective fluorophore Nile red accumulation. Previous reports have NBD-based fluorophores simultaneously despite possibility spectral overlap. In...
Antibiotic activity is limited by the physical construction of Gram-negative cell envelope. Species Burkholderia cepacia complex (Bcc) are known as intrinsically multidrug-resistant opportunistic pathogens with low permeability envelopes. Here, we re-examined a previously performed chemical-genetic screen barcoded transposon mutants in B. cenocepacia K56-2 focus on envelope structural and functional processes. We identified structures mechanistically important for resistance to singular...
Abstract The cell envelope of the Gram-negative Burkholderia cepacia complex (Bcc) presents unique restrictions to antibiotic penetration. As a consequence, Bcc species are notorious for causing recalcitrant multidrug-resistant infections in immunocompromised individuals, such as those living with cystic fibrosis. To systematically identify envelope-associated resistance and susceptibility determinants at genome level, we constructed high-density, randomly-barcoded transposon mutant library...
Abstract Bacteria of the genus Burkholderia include pathogenic mallei, pseudomallei and cepacia complex (Bcc). These Gram-negative pathogens have intrinsic drug resistance, which makes treatment infections difficult. Bcc affects individuals with cystic fibrosis (CF) species B. cenocepacia is associated one worst clinical outcomes. Following repurposing auranofin as an antibacterial against Gram-positive bacteria, we previously synthetized analogs activity Gram-negatives. In this work, show...
Abstract The cell envelope of the Gram-negative Burkholderia cepacia complex (Bcc) presents unique restrictions to antibiotic penetration. As a consequence, Bcc species are notorious for causing recalcitrant multidrug-resistant infections in immunocompromised individuals, such as those living with cystic fibrosis. To systematically identify envelope-associated resistance and susceptibility determinants at genome level, we constructed high-density, randomly-barcoded transposon mutant library...
Abstract Genetic tools are critical to dissecting the mechanisms governing cellular processes, from fundamental physiology pathogenesis. Members of genus Burkholderia have potential for biotechnological applications but can also cause disease in humans with a debilitated immune system. The lack suitable genetic edit GC-rich genomes has hampered exploration useful capacities and understanding pathogenic features. To address this, we developed CRISPR interference (CRISPRi) technology gene...