Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis.
Authors
Arif, Sheikh Mohammed
Floto, R Andres
Blundell, Tom L
Publication Date
2022Journal Title
Front Mol Biosci
ISSN
2296-889X
Publisher
Frontiers Media SA
Volume
9
Language
en
Type
Article
This Version
VoR
Metadata
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Arif, S. M., Floto, R. A., & Blundell, T. L. (2022). Using Structure-guided Fragment-Based Drug Discovery to Target Pseudomonas aeruginosa Infections in Cystic Fibrosis.. Front Mol Biosci, 9 https://doi.org/10.3389/fmolb.2022.857000
Abstract
Cystic fibrosis (CF) is progressive genetic disease that predisposes lungs and other organs to multiple long-lasting microbial infections. Pseudomonas aeruginosa is the most prevalent and deadly pathogen among these microbes. Lung function of CF patients worsens following chronic infections with P. aeruginosa and is associated with increased mortality and morbidity. Emergence of multidrug-resistant, extensively drug-resistant and pandrug-resistant strains of P. aeruginosa due to intrinsic and adaptive antibiotic resistance mechanisms has failed the current anti-pseudomonal antibiotics. Hence new antibacterials are urgently needed to treat P. aeruginosa infections. Structure-guided fragment-based drug discovery (FBDD) is a powerful approach in the field of drug development that has succeeded in delivering six FDA approved drugs over the past 20 years targeting a variety of biological molecules. However, FBDD has not been widely used in the development of anti-pseudomonal molecules. In this review, we first give a brief overview of our structure-guided FBDD pipeline and then give a detailed account of FBDD campaigns to combat P. aeruginosa infections by developing small molecules having either bactericidal or anti-virulence properties. We conclude with a brief overview of the FBDD efforts in our lab at the University of Cambridge towards targeting P. aeruginosa infections.
Keywords
Molecular Biosciences, FBDD, fragment-based drug discovery, antibiotics, cystic fibrosis, Pseudomonas, anti-virulence
Identifiers
857000
External DOI: https://doi.org/10.3389/fmolb.2022.857000
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336055
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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