Strategy to identify molecules with antimicrobial activity by directly assessing the effects of compounds on microbial cell growth in cell-based assays.
In a classical phenotypic screening approach, candidate antimicrobial compounds (hits) are selected based on their ability to affect bacterial growth and survival. If activity is confirmed, further studies are required to identify the specific molecular targets that compounds are interacting with.
An alternative approach is to search for or design compounds that act on a specific bacterial target, a molecule identified as important to bacterial growth and survival. While target-based approaches have been popular, they have not been as successful as anticipated. This has led to a resurgence of interest in phenotypic screens, which give an immediate indication of antibacterial activity.
Phenotypic screens as a renewed approach for drug discovery (Drug Discovery Today, 2013)
Machine learning-powered antibiotics phenotypic drug discovery (Scientific Reports, 2019)
Multi-targeting by monotherapeutic antibacterials (Nature Reviews Drug Discovery, 2007)
Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis (Chemistry & Biology, 2015)
Unconventional screening approaches for antibiotic discovery (Annals of The New York Academy of Sciences, 2015)
REVIVE Webinar: ‘Natural product antibiotics: from traditional screening to novel discovery approaches’ by Olga Genilloud (GARDP, 2019)