A5053151249- Mycobacterium research and diagnosis
- Tuberculosis Research and Epidemiology
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Infectious Diseases and Mycology
- Cancer therapeutics and mechanisms
- RNA and protein synthesis mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- Leprosy Research and Treatment
- Infectious Diseases and Tuberculosis
- Cystic Fibrosis Research Advances
- Bacterial biofilms and quorum sensing
- Yersinia bacterium, plague, ectoparasites research
- Genomics and Phylogenetic Studies
- Diagnosis and treatment of tuberculosis
- Legionella and Acanthamoeba research
- Drug Transport and Resistance Mechanisms
- Enzyme Production and Characterization
- Lung Cancer Diagnosis and Treatment
- Quinazolinone synthesis and applications
Colorado State University
2016-2025
University of Glasgow
2024
The University of Texas Southwestern Medical Center
2023
Southwestern Medical Center
2023
Universidad de Las Américas
2023
University of Kansas
2023
Universidad San Francisco de Quito
2023
Universidad Autónoma de Nuevo León
2022
Swiss Tropical and Public Health Institute
2022
University of Basel
2022
Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of are thought to be critical for mounting a protective anti-mycobacterial immune response determining outcome infection. However, these poorly understood, at least molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast,...
A better understanding of Mycobacterium tuberculosis virulence mechanisms is highly dependent on the design efficient mutagenesis systems. system enabling positive selection insertional mutants having lost delivery vector was developed. It uses ts- sacB vectors, which combine counterselective properties gene and a mycobacterial thermosensitive origin replication can therefore be efficiently counterselected sucrose at 39°C. This methodology allowed construction M. transposition mutant...
A critical feature of Mycobacterium tuberculosis, the causative agent human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing intracellular tubercle bacilli a key requirement efficient treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques lack validated targets. Here, we present development phenotypic cell-based assay that uses automated confocal...
<h3>Background</h3> Despite advances in treatment of cystic fibrosis (CF), pulmonary exacerbations remain common. The aim this study was to determine if frequent are associated with greater declines lung function, or an accelerated time death transplantation adults CF. <h3>Methods</h3> A 3-year prospective cohort conducted on 446 adult patients CF from Ontario, Canada who could spontaneously produce sputum. Patients enrolled 2005 2008 and were stratified into groups based upon their...
' success as a pathogen comes from its ability to evade degradation by macrophages. Normally macrophages clear microorganisms that activate pathogen-recognition receptors (PRRs) through lysosomal-trafficking pathway called "LC3-associated phagocytosis" (LAP). Although
Jump starting pathogen evolution Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of Mycobacterium abscessus emerged in people with cystic fibrosis. Bryant et al. investigated how these mycobacteria evolved into pathogens so quickly (see Perspective by Brugha Spencer). Chronic lung offer plenty evolutionary scope for emergence clones after horizontal gene transfer...
Interactions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to infects DCs through ligation DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) mannose-capped lipoarabinomannan (ManLAM) inhibits binding bacilli lectin, suggesting ManLAM might be DC-SIGN ligand. In present study, we investigated molecular basis by LAM....
The antigen 85 complex of Mycobacterium tuberculosis consists three abundantly secreted proteins. recent characterization a mycoloyltransferase activity associated in vitro with each these antigens suggested that they are potentially important for the building unusual cell envelope mycobacteria. To define physiological role proteins, gene coding 85C was inactivated by transposon mutagenesis. resulting mutant shown to transfer 40% fewer mycolates wall no change types esterifying...
The role of biofilms in the pathogenesis mycobacterial diseases remains largely unknown. Mycobacterium ulcerans, etiological agent Buruli ulcer, a disfiguring disease humans, adopts biofilm-like structure vitro and vivo, displaying an abundant extracellular matrix (ECM) that harbors vesicles. composition ECM differs from classical found other bacterial biofilms. More than 80 proteins are present within this compartment appear to be involved stress responses, respiration, intermediary...
Two-component regulatory signal transduction systems are important elements of the adaptative response prokaryotes to a variety environmental stimuli. Disruption PhoP-PhoR in Mycobacterium tuberculosis dramatically attenuates virulence, implying that this system directly and/or indirectly coordinates expression virulence factors whose identity remains be established. Interestingly, knockingout two-component M. Mt103, dramatic changes colonial morphology, cording properties, and reactivity...
The mycobacterial cell wall core consists of an outer lipid (mycolic acid) layer attached to peptidoglycan via a galactofuranosyl-containing polysaccharide, arabinogalactan. This structural arrangement strongly suggests that galactofuranosyl residues are essential for the growth and viability mycobacteria. Galactofuranosyl formed in nature by ring contraction UDP-galactopyranose UDP-galactofuranose catalyzed enzyme mutase (Glf). In Mycobacterium tuberculosis glf gene overlaps, 1 nucleotide,...
Phosphatidylinositol (PI) and metabolically derived products such as the phosphatidylinositol mannosides linear mature branched lipomannan lipoarabinomannan are prominent phospholipids/lipoglycans of Mycobacterium sp. believed to play important roles in structure physiology bacterium well during host infection. To determine if PI is an essential phospholipid mycobacteria, we identified pgsA gene tuberculosis encoding synthase enzyme constructed a pgsAconditional mutant smegmatis. The ability...
Summary Phospholipases C play a role in the pathogenesis of several bacteria. Mycobacterium tuberculosis , causative agent tuberculosis, possesses four genes encoding putative phospholipases C, plcA plcB plcC and plcD . However, contribution these to virulence is unknown. We constructed single mutants M. each inactivated one plc genes, triple plcABC mutant quadruple plcABCD mutant. The all exhibited lower phospholipase activity than wild‐type parent strain, demonstrating that encode...
The growth of Mycobacterium tuberculosis mutants unable to synthesize phthiocerol dimycocerosates (DIMs) was recently shown be impaired in mouse lungs. However, the precise role these molecules course infection remained determined. Here, we provide evidence that attenuation a DIM-deficient strain takes place during acute phase both lungs and spleen mice, this results part from increased sensitivity mutant cidal activity reactive nitrogen intermediates released by activated macrophages. We...
We examined the function of <i>pimA</i>(Rv2610c) gene, located in vicinity phosphatidylinositol synthase gene genomes <i>Mycobacterium tuberculosis</i>and smegmatis,</i> which encodes a putative mannosyltransferase involved early steps mannoside synthesis. A cell-free assay was developed membranes from <i>M. smegmatis</i> overexpressing <i>pimA</i> incorporate mannose GDP-[<sup>14</sup>C]Man into di- and tri-acylated mono-mannosides. Moreover, crude extracts <i>Escherichia coli</i> producing...
The receptor-like protein kinase PknB from Mycobacterium tuberculosis is encoded by the distal gene in a highly conserved operon, present all actinobacteria, that may control cell shape and division. Genes coding for PknB-like are also found many more distantly related gram-positive bacteria. Here, we report pknB can be disrupted allelic replacement M. saprophyte smegmatis only presence of second functional copy gene. We demonstrate eukaryotic Ser/Thr inhibitors, which inactivate vitro with...
MmpL3, a resistance-nodulation-division (RND) superfamily transporter, has been implicated in the formation of outer membrane Mycobacterium tuberculosis; specifically, MmpL3 is required for export mycolic acids form trehalose monomycolates (TMM) to periplasmic space or M. tuberculosis. Recently, seven series inhibitors identified by whole-cell screening against tuberculosis, including antituberculosis drug candidate SQ109, were shown abolish MmpL3-mediated TMM export. However, this mode...
ABSTRACT A medium containing chlorolactate has been devised to enrich for mutants that are unable utilize lactate growth, and therefore may be defective in cytochrome c. Complementation tests of 6,520 chlorolactate-resistant were obtained spontaneously or induced with UV, ICR-170, nitrosoimidazolidone resulted the identification 195 mutations at cycl locus, which controls primary structure iso-1-cytochrome These mutants, 16 previously isolated, examined total c by spectroscopic methods,...
<h3>Context</h3>Studies from Australia and the United Kingdom have shown that some patients with cystic fibrosis are infected common transmissible strains of Pseudomonas aeruginosa.<h3>Objectives</h3>To determine prevalence incidence infection P aeruginosa whether presence organism was associated adverse clinical outcomes in Canada.<h3>Design, Setting, Participants</h3>Prospective observational cohort study adult cared for at clinics Ontario, Canada, enrollment September 2005 to 2008. Sputum...
Summary Mycobacterium tuberculosis and other pathogenic mycobacterial species produce large amounts of a glycogen‐like α‐glucan that represents the major polysaccharide their outermost capsular layer. To determine role surface‐exposed glucan in physiology virulence these bacteria, orthologues glg genes involved biosynthesis glycogen Escherichia coli were identified M. H37Rv inactivated by allelic replacement. Biochemical analyses mutants complemented strains indicated synthesis involves...