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EcoSal Plus

Domain 11: Antibiotic Mechanisms and Resistance

Ancient Antibiotics, Ancient Resistance

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • Authors: Nicholas Waglechner1,2, Elizabeth J. Culp3,4, and Gerard D. Wright5
  • Editor: Karen Bush6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, L8S 4K1, Canada; 2: These authors contributed equally to this work.; 3: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, L8S 4K1, Canada; 4: These authors contributed equally to this work.; 5: M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, L8S 4K1, Canada; 6: Department of Biology, Indiana University, Bloomington, IN
  • Received 13 October 2020 Accepted 26 January 2021 Published 17 March 2021
  • Address correspondence to Gerard D. Wright, [email protected]
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  • Abstract:

    As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a preantibiotic era requires the discovery of new drugs. While therapeutic use of antibiotics followed by the inevitable selection of resistance is a modern phenomenon, these molecules and the genetic determinants of resistance were in use by environmental microbes long before humans discovered them. In this review, we discuss evidence that antibiotics and resistance were present in the environment before anthropogenic use, describing techniques including direct sampling of ancient DNA and phylogenetic analyses that are used to reconstruct the past. We also pay special attention to the ecological and evolutionary forces that have shaped the natural history of antibiotic biosynthesis, including a discussion of competitive versus signaling roles for antibiotics, proto-resistance, and substrate promiscuity of biosynthetic and resistance enzymes. Finally, by applying an evolutionary lens, we describe concepts governing the origins and evolution of biosynthetic gene clusters and cluster-associated resistance determinants. These insights into microbes’ use of antibiotics in nature, a game they have been playing for millennia, can provide inspiration for discovery technologies and management strategies to combat the growing resistance crisis.

  • Citation: Waglechner N, Culp E, Wright G. 2021. Ancient Antibiotics, Ancient Resistance, EcoSal Plus 2021; doi:10.1128/ecosalplus.ESP-0027-2020

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/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0027-2020
2021-03-17
2021-05-14

Abstract:

As the spread of antibiotic resistance threatens our ability to treat infections, avoiding the return of a preantibiotic era requires the discovery of new drugs. While therapeutic use of antibiotics followed by the inevitable selection of resistance is a modern phenomenon, these molecules and the genetic determinants of resistance were in use by environmental microbes long before humans discovered them. In this review, we discuss evidence that antibiotics and resistance were present in the environment before anthropogenic use, describing techniques including direct sampling of ancient DNA and phylogenetic analyses that are used to reconstruct the past. We also pay special attention to the ecological and evolutionary forces that have shaped the natural history of antibiotic biosynthesis, including a discussion of competitive versus signaling roles for antibiotics, proto-resistance, and substrate promiscuity of biosynthetic and resistance enzymes. Finally, by applying an evolutionary lens, we describe concepts governing the origins and evolution of biosynthetic gene clusters and cluster-associated resistance determinants. These insights into microbes’ use of antibiotics in nature, a game they have been playing for millennia, can provide inspiration for discovery technologies and management strategies to combat the growing resistance crisis.

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Legend indicates the form of evidence for each event marked. See text for details and citation.

Citation: Waglechner N, Culp E, Wright G. 2021. Ancient Antibiotics, Ancient Resistance, EcoSal Plus 2021; doi:10.1128/ecosalplus.ESP-0027-2020
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Methods for studying ancient antibiotics and resistance

Citation: Waglechner N, Culp E, Wright G. 2021. Ancient Antibiotics, Ancient Resistance, EcoSal Plus 2021; doi:10.1128/ecosalplus.ESP-0027-2020

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