Going to extremes: progress in exploring new environments for novel antibiotics

Quinn, Gerry A.; Dyson, Paul

doi:10.1038/s44259-024-00025-8

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Going to extremes: progress in exploring new environments for novel antibiotics

Gerry A. Quinn

, Paul Dyson

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...

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Published in:	npj Antimicrobials and Resistance
ISSN:	2731-8745
Published:	Springer Science and Business Media LLC 2024
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa65922
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first_indexed	2024-03-27T13:33:34Z
last_indexed	2024-03-27T13:33:34Z
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spelling	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
author_id_str_mv	300e3f46b70ae83f563b24f41d00cd17
author_id_fullname_str_mv	300e3f46b70ae83f563b24f41d00cd17_***_Paul Dyson
author	Paul Dyson
author2	Gerry A. Quinn Paul Dyson
format	Journal article
container_title	npj Antimicrobials and Resistance
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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
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	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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Going to extremes: progress in exploring new environments for novel antibiotics

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