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Going to extremes: progress in exploring new environments for novel antibiotics
npj Antimicrobials and Resistance, Volume: 2, Issue: 1
Swansea University Author:
Paul Dyson
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DOI (Published version): 10.1038/s44259-024-00025-8
Abstract
The discoveries of penicillin and streptomycin were pivotal for infection control with the knowledge subsequently being used to enable the discovery of many other antibiotics currently used in clinical practice. These valuable compounds are generally derived from mesophilic soil microorganisms, pred...
Published in: | npj Antimicrobials and Resistance |
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ISSN: | 2731-8745 |
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Springer Science and Business Media LLC
2024
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URI: | https://cronfa.swan.ac.uk/Record/cronfa65922 |
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v2 65922 2024-03-27 Going to extremes: progress in exploring new environments for novel antibiotics 300e3f46b70ae83f563b24f41d00cd17 0000-0002-0558-2666 Paul Dyson Paul Dyson true false 2024-03-27 BMS The discoveries of penicillin and streptomycin were pivotal for infection control with the knowledge subsequently being used to enable the discovery of many other antibiotics currently used in clinical practice. These valuable compounds are generally derived from mesophilic soil microorganisms, predominantly Streptomyces species. Unfortunately, problems with the replication of results suggested that this discovery strategy was no longer viable, motivating a switch to combinatorial chemistry in conjunction with existing screening programmes to derive new antimicrobials. However, the chemical space occupied by these synthetic products is vastly reduced compared to those of natural products. More recent approaches such as using artificial intelligence to ‘design’ synthetic ligands to dock with molecular targets suggest that chemical synthesis is still a promising option for discovery. It is important to employ diverse discovery strategies to combat the worrying increase in antimicrobial resistance (AMR). Here, we reconsider whether nature can supply innovative solutions to recalcitrant infections. Specifically, we assess progress in identifying novel antibiotic-producing organisms from extreme and unusual environments. Many of these organisms have adapted physiologies which often means they produce different repertoires of bioactive metabolites compared to their mesophilic counterparts, including antibiotics. In addition, we examine insights into the regulation of extremotolerant bacterial physiologies that can be harnessed to increase the production of clinically important antibiotics and stimulate the synthesis of new antibiotics in mesophilic microorganisms. Finally, we comment on the insights provided by combinatorial approaches to the treatment of infectious diseases that might enhance the efficacy of antibiotics and reduce the development of AMR. Journal Article npj Antimicrobials and Resistance 2 1 Springer Science and Business Media LLC 2731-8745 25 3 2024 2024-03-25 10.1038/s44259-024-00025-8 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Not Required 2024-04-15T16:23:32.5557532 2024-03-27T13:28:18.2658745 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Gerry A. Quinn 0000-0003-0023-2621 1 Paul Dyson 0000-0002-0558-2666 2 65922__29889__1149ae1a934d49a4b97775269e387727.pdf 65922.pdf 2024-04-03T14:06:54.1207597 Output 1204444 application/pdf Version of Record true This article is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/ |
title |
Going to extremes: progress in exploring new environments for novel antibiotics |
spellingShingle |
Going to extremes: progress in exploring new environments for novel antibiotics Paul Dyson |
title_short |
Going to extremes: progress in exploring new environments for novel antibiotics |
title_full |
Going to extremes: progress in exploring new environments for novel antibiotics |
title_fullStr |
Going to extremes: progress in exploring new environments for novel antibiotics |
title_full_unstemmed |
Going to extremes: progress in exploring new environments for novel antibiotics |
title_sort |
Going to extremes: progress in exploring new environments for novel antibiotics |
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300e3f46b70ae83f563b24f41d00cd17 |
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300e3f46b70ae83f563b24f41d00cd17_***_Paul Dyson |
author |
Paul Dyson |
author2 |
Gerry A. Quinn Paul Dyson |
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Journal article |
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npj Antimicrobials and Resistance |
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2 |
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publishDate |
2024 |
institution |
Swansea University |
issn |
2731-8745 |
doi_str_mv |
10.1038/s44259-024-00025-8 |
publisher |
Springer Science and Business Media LLC |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science |
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description |
The discoveries of penicillin and streptomycin were pivotal for infection control with the knowledge subsequently being used to enable the discovery of many other antibiotics currently used in clinical practice. These valuable compounds are generally derived from mesophilic soil microorganisms, predominantly Streptomyces species. Unfortunately, problems with the replication of results suggested that this discovery strategy was no longer viable, motivating a switch to combinatorial chemistry in conjunction with existing screening programmes to derive new antimicrobials. However, the chemical space occupied by these synthetic products is vastly reduced compared to those of natural products. More recent approaches such as using artificial intelligence to ‘design’ synthetic ligands to dock with molecular targets suggest that chemical synthesis is still a promising option for discovery. It is important to employ diverse discovery strategies to combat the worrying increase in antimicrobial resistance (AMR). Here, we reconsider whether nature can supply innovative solutions to recalcitrant infections. Specifically, we assess progress in identifying novel antibiotic-producing organisms from extreme and unusual environments. Many of these organisms have adapted physiologies which often means they produce different repertoires of bioactive metabolites compared to their mesophilic counterparts, including antibiotics. In addition, we examine insights into the regulation of extremotolerant bacterial physiologies that can be harnessed to increase the production of clinically important antibiotics and stimulate the synthesis of new antibiotics in mesophilic microorganisms. Finally, we comment on the insights provided by combinatorial approaches to the treatment of infectious diseases that might enhance the efficacy of antibiotics and reduce the development of AMR. |
published_date |
2024-03-25T16:23:28Z |
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11.021648 |