Chemical inhibition of Pseudomonas aeruginosa ExsA
Lead Research Organisation:
University of Cambridge
Department Name: Pharmacology
Abstract
Theme: Bioscience for Health
Pseudomonas aeruginosa is a major nosociomal pathogen, and ExsA is a master virulence regulator for the pathogen during acute infections. It is therefore a candidate for the development of anti-virulence drugs, of which none are currently available for P. aeruginosa. Using a computational techniques to predict novel inhibitors which are then characterised in vivo and in vitro this project aims to find lead compounds for future drug development. Relevant investigation into the biology of the signalling cascade is also being undertaken.
Pseudomonas aeruginosa is a major nosociomal pathogen, and ExsA is a master virulence regulator for the pathogen during acute infections. It is therefore a candidate for the development of anti-virulence drugs, of which none are currently available for P. aeruginosa. Using a computational techniques to predict novel inhibitors which are then characterised in vivo and in vitro this project aims to find lead compounds for future drug development. Relevant investigation into the biology of the signalling cascade is also being undertaken.
Organisations
People |
ORCID iD |
| Jack Greenhalgh (Student) |
Publications
Abdelhamid Y
(2019)
Evolutionary plasticity in the allosteric regulator-binding site of pyruvate kinase isoform PykA from Pseudomonas aeruginosa.
in The Journal of biological chemistry
Callejo G
(2020)
In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3.
in Biochemical pharmacology
Greenhalgh JC
(2020)
Proposed model of the Dictyostelium cAMP receptors bound to cAMP.
in Journal of molecular graphics & modelling
Zarkan A
(2020)
Inhibition of indole production increases the activity of quinolone antibiotics against E. coli persisters.
in Scientific reports
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011194/1 | 30/09/2015 | 31/03/2024 | |||
| 1931276 | Studentship | BB/M011194/1 | 30/09/2017 | 01/07/2022 | Jack Greenhalgh |
| NE/W503204/1 | 31/03/2021 | 30/03/2022 | |||
| 1931276 | Studentship | NE/W503204/1 | 30/09/2017 | 01/07/2022 | Jack Greenhalgh |
| Description | Due to the current crisis of antibiotic resistant bacteria new antibacterial agents are urgently needed. The PhD project associated with this award has sort to identify novel small molecules which impair the virulence of the pathogen Pseudomonas aeruginosa. In this regard it appears to have been successful, with a number of novel small molecule inhibitors of the virulence regulating protein ExsA having been identified. The characterisation of these compounds is incomplete as of writing, and further characterisation and confirmation of the positive results obtained so far will be sought during the remainder of the project. |
| Exploitation Route | If and when their action is confirmed the small molecules will provide a lead for further research, ultimately leading to novel therapeutic agents for medical use. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |