- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Antibiotic Resistance in Bacteria
- Trace Elements in Health
- Bacterial Infections and Vaccines
- Bacteriophages and microbial interactions
- Retinal Development and Disorders
- RNA Research and Splicing
- Microbial infections and disease research
- Rabies epidemiology and control
- Antimicrobial Peptides and Activities
- Neonatal and Maternal Infections
- Virology and Viral Diseases
- Click Chemistry and Applications
- Escherichia coli research studies
- Hemoglobinopathies and Related Disorders
- Innovative Microfluidic and Catalytic Techniques Innovation
- Protein Kinase Regulation and GTPase Signaling
- Infant Nutrition and Health
- HIV Research and Treatment
- Heavy Metal Exposure and Toxicity
- Postharvest Quality and Shelf Life Management
- Advanced biosensing and bioanalysis techniques
- Animal Genetics and Reproduction
- Genomics and Phylogenetic Studies
University of Toronto
2013-2024
Canada Research Chairs
2015
University of British Columbia
2007-2012
University of Regensburg
2008
Abstract Invading bacteria from the Neisseriaceae , Acinetobacteriaceae Bordetellaceae and Moraxellaceae families express conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections causative agent of bacterial meningitis, Neisseria meningitidis in a mouse model. We also combine X-ray crystallography molecular dynamics...
Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea HIV. Neisseria gonorrhoeae , which causes gonorrhea, is particularly adept at driving HIV-1 expression, but molecular determinants of this relationship remain undefined. N. liberates a soluble factor that potently induces expression from LTR in coinfected cluster differentiation 4-positive (CD4 + ) T lymphocytes, not previously described innate effector. A genome-wide...
Wax biosynthetic pathways proceed via the elongation of 16:0 acyl-CoA to very long-chain fatty acids (VLCFA), and by further modifications that include reduction primary alcohols formation alkyl esters. We have analyzed esters in stem wax ten cer mutants Arabidopsis thaliana together with corresponding wild types. Alkyl chain lengths between C(38) C(52) were identified, levels ranged from 0.15 microg cm(-2) Wassilewskija (WS) 1.20 cer2. Esters even numbers carbons prevailed, C(42), C(44)...
The surfaces of many Gram-negative bacteria are decorated with soluble proteins anchored to the outer membrane via an acylated N-terminus; these referred as surface lipoproteins or SLPs. In Neisseria meningitidis, SLPs such transferrin-binding protein B (TbpB) and factor-H binding (fHbp) essential for host colonization infection because their roles in iron acquisition immune evasion, respectively. Recently, we identified a family called Slam (Surface lipoprotein assembly modulator) that...
Abstract Mammalian hosts combat bacterial infections through the production of defensive cationic antimicrobial peptides (CAPs). These immune factors are capable directly killing invaders; however, many pathogens have evolved resistance evasion mechanisms such as cell surface modification, CAP sequestration, degradation, or efflux. We discovered that several pathogenic and commensal proteobacteria, including urgent human threat Neisseria gonorrhoeae, secrete a protein (lactoferrin-binding B,...
Lactoferrin binding protein B (LbpB) is a bi-lobed outer membrane-bound lipoprotein that comprises part of the lactoferrin (Lf) receptor complex in Neisseria meningitidis and other Gram-negative pathogens. Recent studies have demonstrated LbpB plays role protecting bacteria from cationic antimicrobial peptides due to large regions rich anionic residues C-terminal lobe. Relative its homolog, transferrin-binding (TbpB), there currently little evidence for iron acquisition relatively structural...
Efficient acquisition of extracellular nutrients is essential for bacterial pathogenesis, however the identities and mechanisms transport many these substrates remain unclear. Here, we investigate predicted iron-binding transporter AfuABC its role in pathogenesis vivo. By crystallographic, biophysical vivo approaches, show that fact a cyclic hexose/heptose-phosphate with high selectivity specificity set ubiquitous metabolites (glucose-6-phosphate, fructose-6-phosphate...
Forkhead-associated (FHA) domains are phosphopeptide recognition modules found in many signaling proteins. The Saccharomyces cerevisiae protein kinase Rad53 is a key regulator of the DNA damage checkpoint and uses its two FHA to interact with multiple binding partners during response. One these Dbf4-dependent (DDK), heterodimer composed Cdc7 regulatory subunit Dbf4. Binding DDK, through N-terminal (FHA1) domain, ultimately inhibits DDK activity, thereby preventing firing late origins. We...
The actin cytoskeleton is a dynamic array of filaments that undergoes rapid remodeling to drive many cellular processes. An essential feature filament the spatio-temporal regulation nucleation. One family nucleators, Diaphanous-related formins, activated by binding small G-proteins such as RhoA. However, RhoA only partially activates suggesting additional factors are required fully activate formin. Here we identify one factor, IQ motif containing GTPase activating protein-1 (IQGAP1), which...
Surface lipoproteins (SLPs) are peripherally attached to the outer leaflet of membrane in many Gram-negative bacteria, playing significant roles nutrient acquisition and immune evasion host. While factors that involved synthesis delivery SLPs inner well characterized, molecular machinery required for movement surface still not fully elucidated. In this study, we investigated translocation a SLP TbpB through Slam1-dependent pathway. Using purified components, developed an vitro assay where...
Klebsiella pneumoniae is a World Health Organization priority pathogen and significant clinical concern for infections of the respiratory urinary tracts due to widespread increasing resistance antimicrobials. In absence vaccine, there an urgent need identify novel targets therapeutic development. Bacterial pathogens, including K. , require d -block metal ion zinc as essential micronutrient, which serves cofactor ~6% proteome. During infection, acquisition necessitates use high affinity...
X-linked juvenile retinoschisis is a heritable condition of the retina in males caused by mutations RS1 gene. Still, cellular function and retina-specific expression are poorly understood. To address latter issue, we characterized minimal promoter driving retina. Binding site prediction, site-directed mutagenesis, reporter assays suggest an essential role two nearby cone-rod homeobox (CRX)-responsive elements (CRE) proximal −177/+32 promoter. Chromatin immunoprecipitation associates vivo...
Bacteria require high-efficiency uptake systems to survive and proliferate in nutrient-limiting environments, such as those found host organisms. ABC transporters the bacterial plasma membrane provide a mechanism for transport of many substrates. In this study, we examine an operon containing periplasmic binding protein Actinobacillus its potential role nutrient acquisition. The electron density map 1.76 Å resolution obtained from crystal structure was best fit with molecular model...
is the leading cause of wound infections in humans following animals' bites or scratches. This bacterium also commonly found respiratory tract many mammals and can serious diseases resulting brutal rapid death infected animals, especially cattle. To prevent these cattle, a subunit-based vaccine utilizing surface lipoprotein PmSLP was developed showed remarkable protection with single dose administration. Here, we report that binds host complement factor I (FI) facilitates cleavage components...
Abstract Surface lipoproteins (SLPs) are peripherally attached to the outer leaflet of membrane in many Gram-negative bacteria, playing significant roles nutrient acquisition and immune evasion host. While factors that involved synthesis delivery SLPs inner well characterized, molecular machineries required for movement surface still not fully elucidated. In this study, we investigated translocation a lipoprotein TbpB through Slam1-dependent pathway. Using purified components, developed an...
Abstract Bacteria require high efficiency uptake systems to survive and proliferate in nutrient limiting environments, such as those found the host. The ABC transporters at bacterial plasma membrane provide a mechanism for transport of many substrates. We recently demonstrated that an AfuABC operon, previously annotated encoding ferrous iron system, is fact cyclic hexose/heptose-phosphate transporter with selectivity specificity these metabolites. In this study, we examine second operon...