A5038744335- Antibiotic Resistance in Bacteria
- Antimicrobial Peptides and Activities
- Click Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Evolution and Genetic Dynamics
- Escherichia coli research studies
- Phenothiazines and Benzothiazines Synthesis and Activities
- Antimicrobial Resistance in Staphylococcus
- Pneumonia and Respiratory Infections
- Antibiotics Pharmacokinetics and Efficacy
- Pneumocystis jirovecii pneumonia detection and treatment
- Advanced Fluorescence Microscopy Techniques
- Bacterial Genetics and Biotechnology
- Gut microbiota and health
- Chemical Synthesis and Analysis
- Antimicrobial agents and applications
- Cytomegalovirus and herpesvirus research
- Biotin and Related Studies
- Chemical Reactions and Mechanisms
- Photodynamic Therapy Research Studies
- Biochemical and Structural Characterization
- Adenosine and Purinergic Signaling
- Synthetic Organic Chemistry Methods
- thermodynamics and calorimetric analyses
- Synthesis and Biological Evaluation
The University of Queensland
2014-2024
Brisbane School of Theology
2019
Mahidol University
2013-2018
Nanyang Technological University
2014
Phenotypic variations between individual microbial cells play a key role in the resistance of pathogens to pharmacotherapies. Nevertheless, little is known about cell individuality antibiotic accumulation. Here, we hypothesise that phenotypic diversification can be driven by fundamental cell-to-cell differences drug transport rates. To test this hypothesis, employed microfluidics-based single-cell microscopy, libraries fluorescent probes and mathematical modelling. This approach allowed us...
The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast nature's control biological pathways via modulation membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation glycopeptide vancomycin selective targeting bacterial membranes. Peptide libraries based on positively charged electrostatic effector...
The polymyxin lipodecapeptides colistin and B have become last resort therapies for infections caused by highly drug-resistant Gram-negative bacteria. Unfortunately, their utility is compromised significant nephrotoxicity polymyxin-resistant bacterial strains. We conducted a systematic activity–toxicity investigation varying eight of the nine amino acid free side chains, preparing over 30 analogues using novel solid-phase synthetic route. Compounds were tested against panel bacteria...
Reduced susceptibility to antimicrobials in Gram-negative bacteria may result from multiple resistance mechanisms, including increased efflux pump activity or reduced porin protein expression. Up-regulation of the system is closely associated with multidrug (MDR). To help investigate role pumps on compound accumulation, a fluorescence-based assay was developed using fluorescent derivatives trimethoprim (TMP), broad-spectrum synthetic antibiotic that inhibits an intracellular target,...
An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised explore structure–activity relationships or conjugated fluorophores generate fluorescent probes. Such probes report bacteria their location in a sample real time. Modelling structures bound cognate 50S ribosome target demonstrates binding same site as is possible. The...
Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as research tools aid in their discovery development. Vancomycin a glycopeptide antibiotic that widely used for the treatment of Gram-positive infections, such life-threatening systemic diseases caused by methicillin-resistant Staphylococcus aureus (MRSA). Here we demonstrate modification vancomycin introduction azide substituent provides versatile intermediate can undergo...
Fluorescent probes derived from the fluoroquinolone antibiotic ciprofloxacin were synthesised using a Cu(<sc>i</sc>)-catalysed azide–alkyne cycloaddition (CuAAC) to link azide derivative with alkyne-substituted green and blue fluorophores.
Antimicrobial resistance threatens the viability of modern medical interventions. There is a dire need developing novel approaches to counter mechanisms employed by starved or slow-growing pathogens that are refractory conventional antimicrobial therapies. peptides have been advocated as potential therapeutic solutions due low levels genetic observed in bacteria against these compounds. However, here we show subpopulations stationary phase Escherichia coli and Pseudomonas aeruginosa survive...
Many bacterial pathogens have now acquired resistance toward commonly used antibiotics, such as the glycopeptide antibiotic vancomycin. In this study, we show that immobilization of vancomycin onto a nanometer-scale solid surface with controlled local density can potentiate action and increase target affinity drug. Magnetic nanoparticles were conjugated model system to investigate relationship between drug potency. We showed remarkable improvement in minimum inhibitory concentration against...
Infections caused by drug resistant bacteria poses a significant threat to global human health, with predicted annual mortality of 10 million 2050. While much attention is focused on developing better therapies, improving diagnosis would allow for rapid initiation optimal treatment, reducing unnecessary antibiotic use and enhancing therapeutic outcomes. There are currently no whole body imaging techniques in clinical that capable specifically identifying bacterial infections. We have...
Abstract A synthesis of the tetrahydropyran (THP) moiety bistramide D has been completed by using cross‐metathesis and kinetically controlled intramolecular oxa‐Michael addition to form ring with excellent trans selectivity. The C9 methyl substituent was introduced an unsaturated sulfone building block, which can be most effectively prepared through a combination diastereoselective allylation alkene isomerisation. effect this group on subsequent reactions mitigated careful choice reaction conditions.
The E. coli dihydrofolate reductase (DHFR) destabilizing domain (DD), which shows promise as a biologic tool and potential gene therapy approach, can be utilized to achieve spatial temporal control of protein abundance in vivo simply by administration its stabilizing ligand, the routinely prescribed antibiotic trimethoprim (TMP). However, chronic TMP use drives development resistance (increasing likelihood subsequent infections) disrupts gut microbiota (linked autoimmune neurodegenerative...
Antimicrobial resistance threatens the viability of modern medical interventions. There is a dire need developing novel approaches to counter mechanisms employed by starved or slow-growing pathogens that are refractory conventional antimicrobial therapies. peptides have been advocated as potential therapeutic solutions due low levels genetic observed in bacteria against these compounds. However, here we show subpopulations stationary phase Escherichia coli and Pseudomonas aeruginosa survive...
Fluorescent antibiotics are multipurpose research tools that readily used for the study of antimicrobial resistance, due to their significant advantage over other methods. To prepare these probes, azide derivatives synthesized, then coupled with alkyne-fluorophores using azide-alkyne dipolar cycloaddition by click chemistry. Following purification, antibiotic activity fluorescent is tested minimum inhibitory concentration assessment. In order bacterial accumulation, either spectrophotometry...
Antimicrobial resistance threatens the viability of modern medical interventions. There is a dire need developing novel approaches to counter mechanisms employed by starved or slow-growing pathogens that are refractory conventional antimicrobial therapies. peptides have been advocated as potential therapeutic solutions due low levels genetic observed in bacteria against these compounds. However, here we show subpopulations stationary phase Escherichia coli and Pseudomonas aeruginosa survive...
Abstract Phenotypic variations between individual microbial cells play a key role in the resistance of pathogens to pharmacotherapies. Nevertheless, little is known about cell individuality antibiotic accumulation. Here we hypothesize that phenotypic diversification can be driven by fundamental cell-to-cell differences drug transport rates. To test this hypothesis, employed microfluidics-based single-cell microscopy, libraries fluorescent probes and mathematical modelling. This approach...
Fluorescent antibiotics are multipurpose research tools that readily used for the study of antimicrobial resistance, due to their significant advantage over other methods. To prepare these probes, azide derivatives synthesized, then coupled with alkyne-fluorophores using azide-alkyne dipolar cycloaddition by click chemistry. Following purification, antibiotic activity fluorescent is tested minimum inhibitory concentration assessment. In order bacterial accumulation, either spectrophotometry...