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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02946-19 |
| _version_ | 1818840780082511872 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:15:37Z |
| format | Article |
| id | doaj.art-9d054285540b4a4da2cf1d3dbac81a9c |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T04:15:37Z |
| publishDate | 2019-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-9d054285540b4a4da2cf1d3dbac81a9c2022-12-21T20:36:19ZengAmerican Society for MicrobiologymBio2150-75112019-12-0110610.1128/mBio.02946-19Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development?Kristofer Wollein Waldetoft0James Gurney1Joseph Lachance2Paul A. Hoskisson3Sam P. Brown4School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USAStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United KingdomSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02946-19actinomycetesantibioticevolutionexperimental evolutionnatural antimicrobial products |
| spellingShingle | Kristofer Wollein Waldetoft James Gurney Joseph Lachance Paul A. Hoskisson Sam P. Brown Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development? mBio actinomycetes antibiotic evolution experimental evolution natural antimicrobial products |
| title | 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_short | Evolving Antibiotics against Resistance: a Potential Platform for Natural Product Development? |
| title_sort | evolving antibiotics against resistance a potential platform for natural product development |
| topic | actinomycetes antibiotic evolution experimental evolution natural antimicrobial products |
| url | https://journals.asm.org/doi/10.1128/mBio.02946-19 |
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