The Science of Antibiotic Discovery.
By Kim Lewis. Cell, 2020
633 citations recorded by the source corpus.
We are experiencing an antimicrobial resistance (AMR) crisis, brought on by the drying up of the antibiotic discovery pipeline and the resulting unchecked spread of resistant pathogens. Traditional methods of screening environmental isolates or compound libraries have not produced a new drug in over 30 years. Antibiotic discovery is uniquely difficult due to a highly restrictive penetration barrier and other mechanisms that allow bacteria to survive in the presence of toxic compounds. In this Perspective, we analyze the challenges facing discovery and discuss an emerging new platform for antibiotic discovery. The penetration barrier makes screening conventional synthetic compound libraries largely impractical, and actinomycetes, the main source of natural product compounds, have been overmined. The emerging platform is based on understanding the rules that guide the permeation of molecules into bacteria and on advances in microbiology, which enable us to identify and access attractive groups of secondary metabolite producers. Establishing this platform will enable reliable production of lead compounds to combat AMR.
Subfields: Clinical Biochemistry, Molecular Medicine, Radiology, Nuclear Medicine and Imaging
View Paper: https://www.semanticscholar.org/paper/79b757db324978cecc8941f87cade313d9acec1f
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Citations in the corpus
- Discovery of a structural class of antibiotics with explainable deep learning (2023, methodology): “We further tested systemic administration of compound 1 in a mouse neutropenic thigh infection model 43 using an oxazolidinone-resistant clinical isolate of MRSA.”