A5038184234- Escherichia coli research studies
- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Bacterial Genetics and Biotechnology
- Tuberculosis Research and Epidemiology
- Synthesis and Biological Evaluation
- Gut microbiota and health
- Bacteriophages and microbial interactions
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Mycobacterium research and diagnosis
- Fungal Plant Pathogen Control
- Bioactive Compounds and Antitumor Agents
- Pneumocystis jirovecii pneumonia detection and treatment
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
- X-ray Diffraction in Crystallography
- Quinazolinone synthesis and applications
- Neuropeptides and Animal Physiology
- Vibrio bacteria research studies
- ATP Synthase and ATPases Research
- Marine Sponges and Natural Products
- Steroid Chemistry and Biochemistry
- Parasitic Infections and Diagnostics
The University of Queensland
2016-2024
Australian e-Health Research Centre
2018-2022
Abstract Antimicrobial resistance threatens the viability of modern medicine, which is largely dependent on successful prevention and treatment bacterial infections. Unfortunately, there are few new therapeutics in clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation antimicrobial activity cannabidiol, main non-psychoactive component cannabis. confirm previous reports Gram-positive expand breadth pathogens tested, including highly resistant...
Summary Bacterial nutrition is an essential aspect of host–pathogen interaction. For the intracellular pathogen Mycobacterium tuberculosis (Mtb), causative agent in humans, fatty acids derived from lipid droplets are considered major carbon source. However, many other soluble nutrients available inside host cells and may be used as alternative sources. Lactate pyruvate abundant human fluids, particularly during inflammation. In this work, we study Mtb metabolism lactate combining classic...
Abstract The ability of Mycobacterium tuberculosis (Mtb) to persist in the host complicates and prolongs (TB) patient chemotherapy. Here we demonstrate that a neglected two-component system (TCS) Mtb, TcrXY, is an autoregulated acid-sensing TCS controls functionally diverse 70-gene regulon required for bacterial persistence. Characterisation two representatives this regulon, Rv3706c Rv3705A , implicate these genes as key determinants survival Mtb vivo by serving important effectors mitigate...
ABSTRACT Urinary tract infection (UTI) is a disease of extremely high incidence in both community and nosocomial settings. UTIs cause significant morbidity mortality, with approximately 150 million cases globally per year. Uropathogenic Escherichia coli (UPEC) the primary UTI generally treated empirically. However, rapidly increasing caused by multidrug-resistant UPEC strains has led to limited available treatment options highlights urgent need develop alternative prevention strategies. In...
Pretomanid and MCC7433, a novel nitroimidazopyrazinone analog, are promising antitubercular agents that belong to the bicyclic nitroimidazole family. Despite possessing high cell permeability, they suffer from poor aqueous solubility require specialized formulations in order be orally bioavailable. To address this limitation, we investigated use of mesoporous silica nanoparticles (MCM-41) as drug carriers. MCM-41 were synthesized using sol–gel method, their surface was further modified with...
E. coli is a multifaceted pathogen of major significance to global human health and an important contributor increasing antibiotic resistance. Given the paucity therapies still effective against multidrug-resistant pathogenic strains, novel treatment prevention strategies are urgently required. In this study, we defined core accessory components genome by examining large collection draft completely sequenced strains available from public databases. This data set was mined employing...
Autotransporters are the largest family of outer membrane and secreted proteins in Gram-negative bacteria. Most autotransporters localised to bacterial surface where they promote colonisation host epithelial surfaces. Here we present crystal structure UpaB, an autotransporter that is known contribute uropathogenic E. coli (UPEC) urinary tract. We provide evidence UpaB can interact with glycosaminoglycans fibronectin. Unique modifications its core β-helical create a groove on one side protein...
Tuberculosis and parasitic diseases, such as giardiasis, amebiasis, leishmaniasis, trypanosomiasis, all urgently require improved treatment options. Recently, it has been shown that antitubercular bicyclic nitroimidazoles pretomanid delamanid have potential repurposed therapeutics for the of visceral leishmaniasis. Here, we show also possesses potent activity against Giardia lamblia Entamoeba histolytica, thus expanding therapeutic nitroimidazooxazines. Synthetic analogues with a novel...
Following the approval of delamanid and pretomanid as new drugs to treat drug-resistant tuberculosis, there is now a renewed interest in bicyclic nitroimidazole scaffolds source therapeutics against infectious diseases. We recently described nitroimidazopyrazinone subclass with promising antitubercular antiparasitic activity, prompting additional efforts generate analogs improved solubility enhanced potency. The key pendant aryl substituent was modified by (i) introducing polar functionality...
Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection the urinary tract and bloodstream, but mechanisms colonisation remain be properly understood. Ucl fimbriae are attachment organelles facilitate adherence. Here, we investigated cellular receptors for expression define molecular Ucl-mediated gut. We demonstrate differential in sequence types associated with disseminated...
Uropathogenic Escherichia coli (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, major UPEC virulence factor, essential for ST131 bladder colonization. The globally dominant sub-lineage strains, clade C/H30-R, possess an ISEc55 insertion in the fimB gene that controls phase-variable fimbriae expression via invertible fimS promoter. We report inactivation these strains causes altered...
New drugs to treat tuberculosis (TB) are urgently needed combat the increase in resistance observed among current first-line and second-line treatments. Here, we propose ketol-acid reductoisomerase (KARI) as a target for anti-TB drug discovery. Twenty-two analogues of IpOHA, an inhibitor plant KARI, were evaluated antimycobacterial agents. The strongest Mycobacterium (Mt) KARI has Ki value 19.7 nM, fivefold more potent than IpOHA (Ki = 97.7 nM). This four other slow- tight-binding inhibitors...
Tuberculosis and parasitic infections continue to impose a significant threat global public health economic growth. There is an urgent need develop new treatments combat these diseases. Here, we report the in vitro vivo profiles of bicyclic nitroimidazole subclass, namely, nitroimidazopyrazinones, against mycobacteria Trypanosoma cruzi. Derivatives with monocyclic side chains were selective Mycobacterium tuberculosis able reduce bacterial load when dosed orally mice. We demonstrated that...
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...
Extra-intestinal pathogenic Escherichia coli (ExPEC) are responsible for diverse infections including meningitis, sepsis and urinary tract infections. The alarming rise in anti-microbial resistance amongst ExPEC complicates treatment has highlighted the need alternative preventive measures. SslE is a lipoprotein secreted by dedicated type II secretion system E. that was first identified as potential vaccine candidate using reverse genetics. Although function protective efficacy of been...
Despite promising efficacy, the clinical use of anti-tubercular therapeutic bedaquiline has been restricted due to safety concerns. To date, limited SAR studies have focused on quinoline ring (A-ring), and as such, we set out explore modifications within this region in an attempt discover new variants with improved profile. We herein report development unique synthetic strategies that facilitated access novel analogues leading discovery activity could be retained following replacement motif...
To date, the clinical use of anti-tubercular therapy bedaquiline has been somewhat limited due to safety concerns. Recent investigations determined that modification B- and C-ring units delivered new diarylquinolines (for example TBAJ-587) with potent activity yet an improved profile reduced affinity for hERG channel. Building on our recent discovery substitution quinoline motif (the A-ring subunit) C5-aryl pyridine groups within analogues led retention activity, we investigated concurrent...
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...
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...
Abstract The ability of Mycobacterium tuberculosis (Mtb) to persist in the host complicates and prolongs (TB) patient chemotherapy. Here we demonstrate that a neglected two-component system (TCS) Mtb, TcrXY, is an autoregulated acid-sensing TCS controls functionally diverse 117-gene regulon required for bacterial persistence. Characterisation two representatives this regulon, Rv3706c Rv3705A , implicate these genes as key determinants survival Mtb vivo by serving important effectors mitigate...
Aminoglycoside antibiotics represent the first class of successful drugs in treatment tuberculosis; however, mycobacteria and other bacterial species possess several drug resistance mechanisms to inactivate these natural products. In past 15 years, a variety amphiphilic aminoglycosides have been shown improved activity against infectious microorganisms subvert mechanisms. Here, we report on four novel synthetic compounds derived from two existing potent antitubercular describe their both...