A5079607770- Tuberculosis Research and Epidemiology
- Immune responses and vaccinations
- Streptococcal Infections and Treatments
- Immune Response and Inflammation
- Antimicrobial Resistance in Staphylococcus
- Immunodeficiency and Autoimmune Disorders
- Bacterial Infections and Vaccines
- Reproductive tract infections research
- Immune Cell Function and Interaction
- Infective Endocarditis Diagnosis and Management
- Neonatal and Maternal Infections
- Influenza Virus Research Studies
- Otolaryngology and Infectious Diseases
- T-cell and B-cell Immunology
- Bacterial Identification and Susceptibility Testing
- Pneumonia and Respiratory Infections
- Syphilis Diagnosis and Treatment
- Diagnosis and treatment of tuberculosis
- Clostridium difficile and Clostridium perfringens research
- Virology and Viral Diseases
University of Toronto
2024-2025
University of Pittsburgh
2019-2025
Western University
2013-2018
Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide
Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for management and control infectious disease. Streptococcus pyogenes a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function force activation T lymphocytes through direct binding lateral surfaces cell receptors class II major histocompatibility complex (MHC-II) molecules. S. invariably encodes...
Blood-based correlates of vaccine-induced protection against tuberculosis (TB) are urgently needed. Here, we analyze the blood transcriptome rhesus macaques immunized with varying doses intravenous (i.v.) BCG followed by Mycobacterium (Mtb) challenge. We use high-dose i.v. recipients for "discovery" and validate our findings in low-dose an independent cohort receiving via different routes. identify seven gene modules, including innate module (module 1) enriched type 1 interferon RIG-I-like...
Tuberculosis (TB) is a major health burden worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose from 5 × 105 CFUs ID to 107 i.v. resulted prevention of Mycobacterium tuberculosis (Mtb) infection TB disease highly susceptible nonhuman primates. Identifying immune mechanisms protection following will facilitate development more effective vaccines against TB. Here, we depleted lymphocyte subsets prior during Mtb...
The globally prominent pathogen Streptococcus pyogenes secretes potent immunomodulatory proteins known as superantigens (SAgs), which engage lateral surfaces of major histocompatibility class II molecules and T-cell receptor (TCR) β-chain variable domains (Vβs). These interactions result in the activation numerous Vβ-specific T cells, is defining activity a SAg. Although streptococcal SAgs are virulence factors scarlet fever toxic shock syndrome, mechanisms by how contribute to life cycle S....
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route dose from 5×10
ABSTRACT Invasive Group A streptococcal (iGAS) infections are rising in Canada and wordwide. The 2022–2023 Ontario iGAS season was among the highest recorded, a trend continuing 2023–2024. We sequenced 38 invasive (blood) 117 non-invasive (pharyngeal) Streptococcus pyogenes clinical isolates from Toronto (January–May 2023) to compare between two cohorts against published sequences determine if any genomic changes accounted for trend. Results demonstrated limited clustering with one small...
ABSTRACT Staphylococcus aureus is a versatile bacterial pathogen that produces T cell-activating toxins known as superantigens (SAgs). Although excessive immune activation by SAgs can induce dysregulated cytokine storm component of what toxic shock syndrome (TSS), the contribution to staphylococcal infection process not well defined. Here, we evaluated role superantigen enterotoxin A (SEA) in bacteremia model using humanized transgenic mice expressing SAg-responsive HLA-DR4 molecules....
Superantigens (SAgs) are potent microbial toxins that function to activate large numbers of T cells in a cell receptor (TCR) Vβ-specific manner, resulting excessive immune system activation. Staphylococcus aureus possesses repertoire distinct SAgs, and the context host-pathogen interactions, staphylococcal SAg research has focused primarily on role these severe invasive diseases. However, contribution SAgs colonization by S. remains unclear. We developed two-week nasal model using...
Retrospective epidemiological studies suggest that the licensed serogroup B meningococcal vaccine 4CMenB (Bexsero) provides some protection against closely related pathogen Neisseria gonorrhoeae in humans. This result has been replicated murine models of gonococcal colonization, with a gonococci-reactive humoral response and more rapid clearance vaginal infection. However, immunization Bexsero consistently elicits robust but does not protect all individuals, so correlates remain undefined....
Abstract Canonical Ag-dependent TCR signaling relies on activation of the src-family tyrosine kinase LCK. However, staphylococcal superantigens can trigger by activating an alternative pathway that is independent LCK and utilizes a Gα11-containing G protein–coupled receptor (GPCR) leading to PLCβ activation. The molecules linking superantigen GPCR are unknown. Using ligand-receptor capture technology LRC-TriCEPS, we identified LAMA2, α2 subunit extracellular matrix protein laminin, as...
Abstract Streptococcus pyogenes is a globally prominent bacterial pathogen that exhibits strict tropism for the human host, yet factors responsible ability of S. to compete within this limited biological niche are not well understood. Using an engineered recombinase-based in vivo expression technology (RIVET) system, we identified -induced promoter region upstream predicted Class IIb bacteriocin system M18 serotype strain MGAS8232. This element was active under vitro laboratory conditions,...
Neisseria gonorrhoeae, which causes the sexually transmitted infection gonorrhea and N. meningitidis, a leading cause of bacterial meningitis septicemia, are closely related human-restricted pathogens that inhabit distinct primary mucosal niches. While successful vaccines against invasive meningococcal disease have been available for decades, rapid rise in antibiotic resistance has led to an urgent need develop effective gonococcal vaccine. Several surface antigens shared among these two...
Fournier's gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, first case caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), strain pyogenic β-hemolytic streptococci that increasingly being recognized as an important human pathogen. describe healthy 59 year-old Caucasian male who presented emergency department with penis scrotum, extension anterior abdominal wall. He underwent urgent surgical debridement his penis, abdomen....
is the causative agent of gonorrhea, an on-going public health problem due in part to lack success with efforts develop efficacious vaccine prevent this sexually transmitted infection. An attractive candidate antigen because its essential function and surface exposure, gonococcal transferrin binding protein B (TbpB) exhibits high levels antigenic variability which poses a significant obstacle evoking broadly protective composition. Here, we utilize phylogenetic information rationally select...
Current guideline recommends the use of two identification methods for Neisseria gonorrhoeae. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) is now used primary and may be sufficient definitive N. The performance three secondary tests (BactiCard, RapID NH NET test) were compared using 45 bacterial isolates, including 37 species. These demonstrated diminished specificity (67% - 88%) gonorrhoeae with MALDI-TOF. Additionally, data from six clinical...
Abstract Background We previously demonstrated in non-human primates (NHP) that intravenous (IV) administration of BCG induces substantial T cell responses and often sterilizing immunity against Mycobacterium tuberculosis (Mtb) infection. Here, we investigated the role populations this unmatched response context necessary immune mechanisms for protection (TB). Methods Beginning 20 weeks after vaccination through end study, rhesus macaques were infused with antibodies to deplete CD4, CD8α, or...
Abstract Our laboratory has demonstrated that intravenous (IV) vaccination with Bacille Calmette-Guerin (BCG; 5x107CFU) provides remarkably robust protection against low-dose Mycobacterium tuberculosis (Mtb) infection in Rhesus macaques (9/10 animals protected [<50 thoracic Mtb CFU]; 100,000-fold reduction compared to intradermal [ID] BCG). IV BCG also resulted a 100-fold increase mycobacterium-specific T cells the bronchoalveolar lavage (BAL) of other routes administration (ID or...
Abstract Our laboratories have shown that intravenous (IV) vaccination with Bacille Calmette-Guerin (BCG; 5×107 CFU) provides robust protection against low-dose Mycobacterium tuberculosis (Mtb) infection in rhesus macaques (9/10 protected [<50 thoracic Mtb CFU]; 100,000-fold reduction compared to intradermal [ID] BCG). IV BCG also resulted a 100-fold increase mycobacterium--specific T cells the airways of animals ID or aerosol administration. To investigate role this protective model,...