A5091905268- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- vaccines and immunoinformatics approaches
- Pneumocystis jirovecii pneumonia detection and treatment
- Inhalation and Respiratory Drug Delivery
- Immune responses and vaccinations
- Immune Response and Inflammation
- Bacteriophages and microbial interactions
- Pneumonia and Respiratory Infections
- Cancer therapeutics and mechanisms
- Immunotherapy and Immune Responses
- Phenothiazines and Benzothiazines Synthesis and Activities
- Pediatric health and respiratory diseases
- Hormonal Regulation and Hypertension
- Membrane Separation and Gas Transport
- Antimicrobial Peptides and Activities
- Synthesis of β-Lactam Compounds
- Antibiotics Pharmacokinetics and Efficacy
- Microbial Natural Products and Biosynthesis
- Parasitic Diseases Research and Treatment
- Advanced Drug Delivery Systems
- Chemical Synthesis and Analysis
- Pharmacogenetics and Drug Metabolism
- Renin-Angiotensin System Studies
- Drug Solubulity and Delivery Systems
Centenary Institute
2017-2025
The University of Sydney
2014-2025
Royal Prince Alfred Hospital
2024
University of Technology Sydney
2024
Tuberculosis (TB), caused by Mycobacterium tuberculosis, results in approximately 1.6 million deaths annually. BCG is the only TB vaccine currently use and offers variable protection; however, development of more effective vaccines hindered a lack defined correlates protection (CoP) against M. tuberculosis. Pulmonary delivery promising strategy since it may promote lung-resident immune memory that can respond rapidly to respiratory infection. In this study, CysVac2, subunit protein...
Significance Tuberculosis is the leading cause of death worldwide from a single infectious agent, but vaccines developed to date have limited efficacy and pose safety concerns. Protein-based are safe option usually require powerful adjuvants. We present examples fully synthetic, self-adjuvanted protein vaccine constructs. These comprise low-dose immune-stimulating adjuvant, covalently fused ESAT6 Mycobacterium tuberculosis , causative agent tuberculosis. When administered by inhalation,...
The significant global impact of tuberculosis (TB) on human health is exacerbated by the increasing prevalence multi-drug resistant (MDR-TB) and challenges novel drug discovery for treatment drug-susceptible drug-resistant strains M. tuberculosis. Rifampicin a key first-line TB rifampicin resistance major obstacle to treating MDR-TB. Utilising existing antimicrobial drugs supplement combination therapy overcome promising solution due their widespread availability proven clinical safety...
T-lymphocytes are critical for protection against respiratory infections, such as Mycobacterium tuberculosis and influenza virus, with chemokine receptors playing an important role in directing these cells to the lungs. CXCR6 is expressed by activated its ligand, CXCL16, constitutively bronchial epithelia, suggesting a T-lymphocyte recruitment retention. However, it unknown whether required responses pulmonary infection, particularly on CD4+ T-lymphocytes. Analysis of CXCR6-reporter mice...
Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against Mycobacterium tuberculosis (Mtb), the causative agent of (TB). Herein, we describe design synthesis a library analogues these two using an efficient solid-phase late-stage macrolactamization strategy. Lead possessed potent Mtb in vitro (minimum inhibitory concentration 125-500 nM) were shown to inhibit protein degradation by mycobacterial ClpC1-ClpP1P2 protease with...
Tuberculosis remains a leading cause of mortality among infectious diseases worldwide, prompting the need to discover new drugs fight this disease. We report here design, synthesis, and antimycobacterial activity isatin-mono/bis-isoniazid hybrids. Most compounds exhibited very high against Mycobacterium tuberculosis, with MICs in range 0.195 0.39 μg/ml, exerted more potent bactericidal effect than standard antitubercular drug isoniazid (INH). Importantly, these were found be well tolerated...
In this study, we demonstrate that B-type natriuretic peptide (BNP) opposed angiotensin II (Ang II)-stimulated de novo cholesterol biosynthesis, cellular uptake, transfer to the inner mitochondrial membrane, and steroidogenesis, which are required for biosynthesis of steroid hormones such as aldosterone cortisol in primary human adrenocortical cells. BNP dose-dependently stimulated intracellular cGMP production with an EC50 11 nm, implying cells express guanylyl cyclase A receptor. cDNA...
Recent studies have demonstrated that efflux pumps of Mycobacterium tuberculosis (M. tb) provide a crucial mechanism in the development drug resistant to antimycobacterial drugs. Drugs inhibit these pumps, such as verapamil, shown potential enhancing treatment success. We therefore hypothesized combined inhaled administration verapamil and first-line rifamycin antibiotic will further improve efficacy. An inhalable dry powder consisting amorphous crystalline rifapentine with l-leucine an...
Abstract Immunogenic carrier proteins such as the non‐toxic diphtheria toxin variant, cross‐reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines inherently expensive due laborious manufacturing steps. Here, this work develops a particulate platform based on using engineered Escherichia coli assemble CRM197‐antigen fusion into discrete submicron‐sized particles. This approach enables...
Currently available vaccines fail to provide consistent protection against tuberculosis (TB). New, improved are urgently needed for controlling the disease. The mycobacterial antigen fusions H4 (Ag85B-TB10.4) and H28 (Ag85B-TB10.4-Rv2660c) have been shown be very immunogenic considered as potential candidates TB vaccine development. However, soluble protein often poorly immunogenic, but augmented immune responses can induced when selected antigens delivered in particulate form. This study...
Tuberculosis afflicts an estimated 2 billion people worldwide and causes 1.3 million deaths annually. Chemotherapeutic solutions rely on drugs developed many years ago, with only one new therapeutic having been approved in the last 40 years. Given rise of drug-resistant strains, there is urgent need for development a more robust drug pipeline. GlaxoSmithKline recently placed structures activities 177 novel anti-tubercular leads public domain, as well results ongoing optimisation some series....
Abstract Mycobacterium tuberculosis infects over 10 million people annually and kills more each year than any other human pathogen. The current (TB) vaccine is only partially effective in preventing infection, while TB treatment problematic terms of length, complexity patient compliance. There an urgent need for new drugs to combat the burden disease natural environment has re-emerged as a rich source bioactive molecules development lead compounds. In this study, one species marine sponge...
Mycobacterium tuberculosis is a major human pathogen, and new vaccines are needed to prevent transmission. Mucosal vaccination may confer protection against M. by stimulating tissue-resident memory (TRM) CD4+ T cells in the lungs. The chemokine receptor CXCR3 promotes lung recruitment of cells, but its role TRM development unknown. This study demonstrates recombinant influenza A virus vaccine PR8.p25, expressing immunodominant cell epitope p25, induces expression on p25-specific lungs so...
<title>Abstract</title> The protein quality control system is a promising and largely untapped mycobacterial target for the discovery of novel antibiotics. ClpC1:ClpP1P2 protease an essential component involved in both regulatory stress-related degradation. Several cyclic peptide natural products have been discovered, including ecumicin, ilamycins cyclomarin, which bind ClpC1 chaperone possess potent antimycobacterial activity. This has led to significant interest these molecules, more...
Abstract Background The enormous burden of tuberculosis (TB) worldwide is a major challenge to human health, but the costs and risks associated with novel drug discovery have limited treatment options for patients. Repurposing existing antimicrobial drugs offers promising avenue expand TB possibilities. This study aimed explore activity synergy beta-lactams in combination beta-lactamase inhibitor, which been underutilized date. Methods Based on inhibitory concentration, oral bioavailability,...
Abstract The development of safe and effective adjuvants is a critical goal vaccine programs. In this report, we defined the immunostimulatory profile protective effect against aerosol Mycobacterium tuberculosis infection formulations incorporating semi-crystalline adjuvant δ-inulin (Advax). Advax formulated with CpG oligonucleotide QS-21 saponin (Advax CpQS ) was most combination, demonstrated by capacity CysVac2/Advax to significantly reduce bacterial burden in lungs M. -infected mice....
Bis-substituted cyclam derivatives have recently emerged as a promising new class of antibacterial agents, displaying excellent activity against drug-resistant Mycobacterium tuberculosis ( Mtb ). Carborane pendants enhance this activity.