A5063522727- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Bioactive Compounds and Antitumor Agents
- Mycobacterium research and diagnosis
- Antimicrobial Resistance in Staphylococcus
- Biochemical and Structural Characterization
- Bacterial biofilms and quorum sensing
- Neutropenia and Cancer Infections
- DNA and Nucleic Acid Chemistry
- Synthesis and biological activity
- Biochemical and Molecular Research
- Biochemical Acid Research Studies
- Cancer Research and Treatments
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Eicosanoids and Hypertension Pharmacology
- Pharmacogenetics and Drug Metabolism
- Tuberculosis Research and Epidemiology
- Blood transfusion and management
- Drug Transport and Resistance Mechanisms
- Microbial Natural Products and Biosynthesis
Norwich Research Park
2016-2024
John Innes Centre
2016-2024
University of East Anglia
2020-2023
University of Birmingham
2022-2023
University of Bradford
2023
European Molecular Biology Laboratory
2020
We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring 10-fold improved aqueous solubility, inhibition topoisomerase IV A. P. decreased human IIα, no cross-resistance to novobiocin. Cocrystal structures 1 in complex Escherichia coli GyrB24 (S)-27 GyrB23 aeruginosa revealed their binding...
BACKGROUND: Currently, the maximum outdate for platelets is 5 days, because of increasing chance bacterial growth over time. Various methods rapid detection contamination blood components have been described, with mixed results and no general acceptance. A recently molecular biologic approach involves a chemiluminescence‐ linked universal DNA probe to highly conserved region ribosomal RNA (rRNA). STUDY DESIGN AND METHODS: multicenter trial chemiluminescence‐linked rRNA in platelet...
N-(Benzothiazole-2-yl)pyrrolamide DNA gyrase inhibitors with benzyl or phenethyl substituents attached to position 3 of the benzothiazole ring carboxamide nitrogen atom were prepared and studied for their inhibition Escherichia coli by supercoiling assay. Compared bearing at 4 ring, was attenuated moving substituent further atom. A co-crystal structure (Z)-3-benzyl-2-((4,5-dibromo-1H-pyrrole-2-carbonyl)imino)-2,3-dihydrobenzo[d]-thiazole-6-carboxylic acid (I) in complex E. GyrB24 (ATPase...
Abstract Objectives To evaluate the efficacy of two novel compounds against mycobacteria and determine molecular basis their action on DNA gyrase using structural mechanistic approaches. Methods Redx03863 Redx04739 were tested in antibacterial assays, also target, gyrase, supercoiling ATPase assays. X-ray crystallography was used to structure B protein sub-domain from Mycobacterium smegmatis complexed with aminocoumarin drug novobiocin, structures same domain thermoresistibile Redx03863....
We present a new series of 2-aminobenzothiazole-based DNA gyrase B inhibitors with promising activity against ESKAPE bacterial pathogens. Based on the binding information extracted from cocrystal structure inhibitor A, in complex Escherichia coli GyrB24, we expanded chemical space benzothiazole-based to C5 position benzothiazole ring. In particular, compound E showed low nanomolar inhibition (IC50 < 10 nM) and broad-spectrum antibacterial pathogens belonging group, minimum inhibitory...
Adhesive interactions between Staphylococcus aureus and the host rely on cell-wall-anchored proteins such as fibronectin-binding protein B (FnBPB). Recently we showed that FnBPB expressed by clonal complex (CC) 1 isolates of S. mediates bacterial adhesion to corneodesmosin. The proposed ligand-binding region CC1-type shares just 60 % amino acid identity with archetypal from CC8. Here investigated ligand binding biofilm formation FnBPB. We found A domain binds fibrinogen corneodesmosin...
Abstract The human pathogen Mycobacterium tuberculosis is the causative agent of resulting in over 1 million fatalities every year, despite decades research into development new anti-TB compounds. Unlike most other organisms M. has six putative genes for epoxide hydrolases (EH) α/β-hydrolase family with little known about their individual substrates, suggesting functional significance these to organism. Due role detoxification, EH’s have been identified as potential drug targets. Here, we...
Abstract Antibiotic resistance is a major global issue in healthcare and understanding the drivers of key developing effective strategies to counter it. Many non-antibiotic drugs, such as cancer chemotherapy can have antimicrobial properties but their effects on bacteria context infection drug only recently begun be explored. Here we investigate 5-fluorouracil (5-FU) common human commensal pathogen Staphylococcus aureus . 5-FU metabolized by S. ultimately results inhibition ThyA, involved...
DNA topoisomerases have been described as ‘the magicians of the world’, somehow allowing strands to pass through each other. These ingenious enzymes are both essential and potentially dangerous, any interruption in their breakage-reunion reactions can lead chromosome breaks cell death. This has led development important targets for antibacterial anti-cancer chemotherapy.
Abstract Adhesive interactions between Staphylococcus aureus and the host rely on cell wall-anchored proteins such as fibronectin binding protein B (FnBPB). Recently we showed that FnBPB expressed by clonal complex (CC) 1 isolates of S. mediates bacterial adhesion to corneodesmosin. The proposed ligand region CC1-type shares just 60% amino acid identity with archetypal from CC8. Here investigated biofilm formation FnBPB. We found A domain binds fibrinogen corneodesmosin identified residues...
The OXA β-lactamases are responsible for hydrolysing β-lactam antibiotics and contribute to the multidrug-resistant phenotype of several major human pathogens. OXAAb enzymes intrinsic Acinetobacter baumannii can confer resistance carbapenem antibiotics. Here we determined structure most prevalent enzyme, OXA-66. OXA-66 was solved at a resolution 2.1 Å found be very similar OXA-51, only other enzyme that has had its solved. Our data contained one molecule per asymmetric unit, analysis...