A5054669832- Tuberculosis Research and Epidemiology
- Autophagy in Disease and Therapy
- Mycobacterium research and diagnosis
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Immune cells in cancer
- Biochemical and Molecular Research
- Immune Cell Function and Interaction
- Escherichia coli research studies
- Glycosylation and Glycoproteins Research
- Bacteriophages and microbial interactions
- Quinazolinone synthesis and applications
- Microbial Natural Products and Biosynthesis
- Complement system in diseases
- CRISPR and Genetic Engineering
- Adenosine and Purinergic Signaling
- Vibrio bacteria research studies
- Infectious Diseases and Mycology
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- Insect symbiosis and bacterial influences
- Marine Sponges and Natural Products
- Bacterial Genetics and Biotechnology
- HIV Research and Treatment
- Immunodeficiency and Autoimmune Disorders
The University of Queensland
2018-2024
The University of Texas Medical Branch at Galveston
2020-2022
Griffith University
2016
University of Toronto
1999-2000
University of Waterloo
2000
Centre for Addiction and Mental Health
1999
Autophagy is a fundamental cellular process that has important roles in innate and adaptive immunity against broad range of microbes. Many pathogenic microbes have evolved mechanisms to evade or exploit autophagy. It been previously demonstrated induction autophagy can suppress the intracellular survival mycobacteria, several PE_PGRS family proteins Mycobacterium tuberculosis proposed act as inhibitors promote mycobacterial survival. However, by which these effectors inhibit not defined....
Autophagy is an ubiquitous homeostatic pathway in mammalian cells and plays a significant role host immunity. Substantial evidence indicates that the ability of Mycobacterium tuberculosis (Mtb) to successfully evade immune responses partially due inhibition autophagic pathways. Our previous screening Mtb transposon mutants identified PPE51 protein as important autophagy-inhibiting effector. We found expression PPE51, either by infecting bacteria or direct cells, suppressed potent...
Drug-resistant strains of Mycobacterium tuberculosis are a major global health problem. Resistance to the front-line antibiotic isoniazid is often associated with mutations in katG-encoded bifunctional catalase-peroxidase. We hypothesise that perturbed KatG activity would generate collateral vulnerabilities isoniazid-resistant katG mutants, providing potential pathway targets combat resistance. Whole genome CRISPRi screens, transcriptomics, and metabolomics were used genome-wide map cellular...
The interaction of host cells with mycobacteria is complex and can lead to multiple outcomes ranging from bacterial clearance progressive or latent infection. Autophagy recognized as one component cell responses that has an essential role in innate adaptive immunity intracellular bacteria. Many microbes, including
Antibiotic resistance poses a significant hurdle in combating global public health crises, prompting the development of novel therapeutics. Strategies to enhance intracellular killing mycobacteria by targeting host defense mechanisms offer numerous beneficial effects, which include reducing cytotoxicity caused current lengthy anti-tubercular treatment regimens and slowing or circumventing multidrug-resistant strains. The pathogen Mycobacterium tuberculosis infects macrophages exploits...
ABSTRACT Melioidosis, caused by the bacterium Burkholderia pseudomallei , is an often severe infection that regularly involves respiratory disease following inhalation exposure. Intranasal (i.n.) inoculation of mice represents experimental approach used to study contributions bacterial capsular polysaccharide I (CPS I) virulence during acute disease. We aerosol delivery B. establish in and studied CPS context innate immune responses. improved survival vivo triggered multiple cytokine...
Homologous alignment cloning (HAC) is a rapid method of molecular that facilitates low-cost, highly efficient polymerase chain reaction products into any plasmid vector in approximately 2 min. HAC insert integration due to sequence strategy, by way short, vector-specific homology tails appended during amplification. Simultaneous exposure single-stranded fragment ends, utilising the 3'→5' exonuclease activity T4 DNA polymerase, creates overlapping homologous on each molecule. The quenched...
Autophagy is an important mechanism for promoting Mycobacterium clearance from macrophages. Pathogenic and non-pathogenic mycobacterium can activate the mTOR pathway while simultaneously inducing autophagy. M. tuberculosis bovis BCG inhibit autophagy favor intracellular bacteria survival.We observed that pre-infection of live or heat-killed could prevent induced by pharmacological activators smegmatis, a strong autophagy-inducing mycobacterium. BCG-derived lipids are responsible inhibition....
Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and offer effective additive therapeutic options. High-throughput screening subset NatureBank marine fraction library (n = 2000) identified sample derived from Australian sponge belonging order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation organic extract this led purification...
The current vaccine for tuberculosis (TB) is a live attenuated strain of Mycobacterium bovis (BCG) and while effective at reducing the potential disseminated TB in young children its disease protection rates adults highly variable it confers little against latent TB. With these limitations new desperately needed. We investigated efficacy three members mycobacterial membrane protein Large (MmpL) family as subunit vaccines MmpLs are large, multifunctional integral proteins, such recalcitrant...
Simple alkyl-sulfonylacetamides have potent antitubercular activity and significantly decrease mycolic acid levels in mycobacteria. Although these compounds were originally designed to inhibit the ketoacyl synthase domain of fatty synthase, structure-activity relationships biochemical evidence do not fully support as target. In 2004, an enzyme family involved activation transfer acids acyl-adenylates was identified mycobacteria, separate from universal acetyl-CoA carrier mechanism. These...
Mycobacterium ulcerans is the causative agent of Buruli ulcer (BU), third most common mycobacterial infection. Virulent M. secretes mycolactone, a polyketide toxin. Most observations infection are described as an extracellular milieu in form necrotic ulcer. While some evidence exists intracellular life cycle for during infection, exact role that mycolactone plays this process poorly understood. Many previous studies have relied upon addition purified to cell-culture systems study its...
Abstract Mycobacterium tuberculosis (Mtb), the causative agent of (TB), is responsible for approximately 10 million new infections and 1.5 deaths each year. Pattern recognition receptors (PRRs) expressed on surface macrophages play an important role in orchestrating immune response to pathogens. Amongst these, C-type lectin (CLRs) are PRR system that increasingly understood mediate innate immunity mycobacteria. We recently described a anti-bacterial anti-inflammatory macrophage...
Abstract Macrophage plasticity and functional activation are critical to the broad array of macrophage-mediated functions that help determine disease outcomes. galactose-type lectin (MGL), a type-2 C-type receptor (CLR) primarily expressed on myeloid cells, has been shown play an anti-inflammatory role in innate response some infectious agents. Our lab recently demonstrated MGL-1 contributes antimicrobial murine model experimental tuberculosis. We further observe MGL-2 expression by RAW...