Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?

ABSTRACT To avoid an antibiotic resistance crisis, we need to develop antibiotics at a pace that matches the rate of evolution of resistance. However, the complex functions performed by antibiotics—combining, e.g., penetration of membranes, counteraction of resistance mechanisms, and interaction wit...

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Autores principales:	Kristofer Wollein Waldetoft, James Gurney, Joseph Lachance, Paul A. Hoskisson, Sam P. Brown
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	actinomycetes antibiotic evolution experimental evolution natural antimicrobial products Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9d054285540b4a4da2cf1d3dbac81a9c
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id	oai:doaj.org-article:9d054285540b4a4da2cf1d3dbac81a9c
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spelling	oai:doaj.org-article:9d054285540b4a4da2cf1d3dbac81a9c2021-11-15T15:54:44ZEvolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?10.1128/mBio.02946-192150-7511https://doaj.org/article/9d054285540b4a4da2cf1d3dbac81a9c2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02946-19https://doaj.org/toc/2150-7511ABSTRACT To avoid an antibiotic resistance crisis, we need to develop antibiotics at a pace that matches the rate of evolution of resistance. However, the complex functions performed by antibiotics—combining, e.g., penetration of membranes, counteraction of resistance mechanisms, and interaction with molecular targets—have proven hard to achieve with current methods for drug development, including target-based screening and rational design. Here, we argue that we can meet the evolution of resistance in the clinic with evolution of antibiotics in the laboratory. On the basis of the results of experimental evolution studies of microbes in general and antibiotic production in Actinobacteria in particular, we propose methodology for evolving antibiotics to circumvent mechanisms of resistance. This exploits the ability of evolution to find solutions to complex problems without a need for design. We review evolutionary theory critical to this approach and argue that it is feasible and has important advantages over current methods for antibiotic discovery.Kristofer Wollein WaldetoftJames GurneyJoseph LachancePaul A. HoskissonSam P. BrownAmerican Society for Microbiologyarticleactinomycetesantibioticevolutionexperimental evolutionnatural antimicrobial productsMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	actinomycetes antibiotic evolution experimental evolution natural antimicrobial products Microbiology QR1-502
spellingShingle	actinomycetes antibiotic evolution experimental evolution natural antimicrobial products Microbiology QR1-502 Kristofer Wollein Waldetoft James Gurney Joseph Lachance Paul A. Hoskisson Sam P. Brown Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
description	ABSTRACT To avoid an antibiotic resistance crisis, we need to develop antibiotics at a pace that matches the rate of evolution of resistance. However, the complex functions performed by antibiotics—combining, e.g., penetration of membranes, counteraction of resistance mechanisms, and interaction with molecular targets—have proven hard to achieve with current methods for drug development, including target-based screening and rational design. Here, we argue that we can meet the evolution of resistance in the clinic with evolution of antibiotics in the laboratory. On the basis of the results of experimental evolution studies of microbes in general and antibiotic production in Actinobacteria in particular, we propose methodology for evolving antibiotics to circumvent mechanisms of resistance. This exploits the ability of evolution to find solutions to complex problems without a need for design. We review evolutionary theory critical to this approach and argue that it is feasible and has important advantages over current methods for antibiotic discovery.
format	article
author	Kristofer Wollein Waldetoft James Gurney Joseph Lachance Paul A. Hoskisson Sam P. Brown
author_facet	Kristofer Wollein Waldetoft James Gurney Joseph Lachance Paul A. Hoskisson Sam P. Brown
author_sort	Kristofer Wollein Waldetoft
title	Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
title_short	Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
title_full	Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
title_fullStr	Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
title_full_unstemmed	Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?
title_sort	evolving antibiotics against resistance: a potential platform for natural product development?
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9d054285540b4a4da2cf1d3dbac81a9c
work_keys_str_mv	AT kristoferwolleinwaldetoft evolvingantibioticsagainstresistanceapotentialplatformfornaturalproductdevelopment AT jamesgurney evolvingantibioticsagainstresistanceapotentialplatformfornaturalproductdevelopment AT josephlachance evolvingantibioticsagainstresistanceapotentialplatformfornaturalproductdevelopment AT paulahoskisson evolvingantibioticsagainstresistanceapotentialplatformfornaturalproductdevelopment AT sampbrown evolvingantibioticsagainstresistanceapotentialplatformfornaturalproductdevelopment
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Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?

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