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Article ; Online: Overcoming drug resistance, the natural way.

Hutchings, Matthew I / Duncan, Katherine R

2022 Volume 30, Issue 3, Page(s) 273–274

Abstract: Colistin is an antibiotic of last resort for treating Gram-negative bacterial infections, but resistance is spreading rapidly. In a recent issue of Nature, Wang et al. use genome mining to identify and synthesize a natural variant that bypasses colistin ... ...

Abstract	Colistin is an antibiotic of last resort for treating Gram-negative bacterial infections, but resistance is spreading rapidly. In a recent issue of Nature, Wang et al. use genome mining to identify and synthesize a natural variant that bypasses colistin resistance and offers new hope for tackling antimicrobial resistance.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Colistin/pharmacology ; Colistin/therapeutic use ; Drug Resistance ; Gram-Negative Bacterial Infections/drug therapy ; Humans
Chemical Substances	Anti-Bacterial Agents ; Colistin (Z67X93HJG1)
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2022.02.008
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Article: Future directions for the discovery of antibiotics from actinomycete bacteria.

Devine, Rebecca / Hutchings, Matthew I / Holmes, Neil A

Emerging topics in life sciences

2021 Volume 1, Issue 1, Page(s) 1–12

Abstract: Antimicrobial resistance (AMR) is a growing societal problem, and without new anti-infective drugs, the UK government-commissioned O'Neil report has predicted that infectious disease will claim the lives of an additional 10 million people a year ... ...

Abstract	Antimicrobial resistance (AMR) is a growing societal problem, and without new anti-infective drugs, the UK government-commissioned O'Neil report has predicted that infectious disease will claim the lives of an additional 10 million people a year worldwide by 2050. Almost all the antibiotics currently in clinical use are derived from the secondary metabolites of a group of filamentous soil bacteria called actinomycetes, most notably in the genus Streptomyces. Unfortunately, the discovery of these strains and their natural products (NPs) peaked in the 1950s and was then largely abandoned, partly due to the repeated rediscovery of known strains and compounds. Attention turned instead to rational target-based drug design, but this was largely unsuccessful and few new antibiotics have made it to clinic in the last 60 years. In the early 2000s, however, genome sequencing of the first Streptomyces species reinvigorated interest in NP discovery because it revealed the presence of numerous cryptic NP biosynthetic gene clusters that are not expressed in the laboratory. Here, we describe how the use of new technologies, including improved culture-dependent and -independent techniques, combined with searching underexplored environments, promises to identify a new generation of NP antibiotics from actinomycete bacteria.
Language	English
Publishing date	2021-01-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2882721-1
ISSN	2397-8554 ; 2397-8554 ; 2397-8562
ISSN (online)	2397-8554
ISSN	2397-8554 ; 2397-8562
DOI	10.1042/ETLS20160014
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Article ; Online: Antibiotics from rare actinomycetes, beyond the genus Streptomyces.

Parra, Jonathan / Beaton, Ainsley / Seipke, Ryan F / Wilkinson, Barrie / Hutchings, Matthew I / Duncan, Katherine R

Current opinion in microbiology

2023 Volume 76, Page(s) 102385

Abstract: Throughout the golden age of antibiotic discovery, Streptomyces have been unsurpassed for their ability to produce bioactive metabolites. Yet, this success has been hampered by rediscovery. As we enter a new stage of biodiscovery, omics data and existing ...

Abstract	Throughout the golden age of antibiotic discovery, Streptomyces have been unsurpassed for their ability to produce bioactive metabolites. Yet, this success has been hampered by rediscovery. As we enter a new stage of biodiscovery, omics data and existing scientific repositories can enable informed choices on the biodiversity that may yield novel antibiotics. Here, we focus on the chemical potential of rare actinomycetes, defined as bacteria within the order Actinomycetales, but not belonging to the genus Streptomyces. They are named as such due to their less-frequent isolation under standard laboratory practices, yet there is increasing evidence to suggest these biologically diverse genera harbour considerable biosynthetic and chemical diversity. In this review, we focus on examples of successful isolation and genera that have been the focus of more concentrated biodiscovery efforts, we survey the representation of rare actinomycete taxa, compared with Streptomyces, across natural product data repositories in addition to its biosynthetic potential. This is followed by an overview of clinically useful drugs produced by rare actinomycetes and considerations for future biodiscovery efforts. There is much to learn about these underexplored taxa, and mounting evidence suggests that they are a fruitful avenue for the discovery of novel antimicrobials.
MeSH term(s)	Actinobacteria/genetics ; Actinobacteria/metabolism ; Actinomyces ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism ; Streptomyces/genetics ; Biodiversity
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2023.102385
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Article ; Online: Evidence of a role for CutRS and actinorhodin in the secretion stress response in

McLean, Thomas C / Beaton, Ainsley D M / Martins, Carlo / Saalbach, Gerhard / Chandra, Govind / Wilkinson, Barrie / Hutchings, Matthew I

Microbiology (Reading, England)

2023 Volume 169, Issue 7

Abstract: CutRS was the first two-component system to be identified ... ...

Abstract	CutRS was the first two-component system to be identified in
MeSH term(s)	Streptomyces coelicolor/genetics ; Streptomyces coelicolor/metabolism ; Transcription Factors/genetics ; Streptomyces/metabolism ; Anti-Bacterial Agents/pharmacology ; Disulfides/metabolism ; Gene Expression Regulation, Bacterial
Chemical Substances	actinorhodin (G4HH387T6Z) ; Transcription Factors ; Anti-Bacterial Agents ; Disulfides
Language	English
Publishing date	2023-07-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180712-x
ISSN	1465-2080 ; 1350-0872
ISSN (online)	1465-2080
ISSN	1350-0872
DOI	10.1099/mic.0.001358
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Article ; Online: Editorial overview: Antimicrobials: Tackling AMR in the 21st century.

Hutchings, Matthew I / Truman, Andrew W / Wilkinson, Barrie

Current opinion in microbiology

2019 Volume 51, Page(s) iii–v

MeSH term(s)	Animals ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacteria/genetics ; Bacterial Infections/diagnosis ; Bacterial Infections/drug therapy ; Bacterial Infections/microbiology ; Drug Resistance, Bacterial ; Humans
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2019-12-09
Publishing country	England
Document type	Editorial ; Introductory Journal Article
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2019.11.004
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Article ; Online: Antibiotics: past, present and future.

Hutchings, Matthew I / Truman, Andrew W / Wilkinson, Barrie

Current opinion in microbiology

2019 Volume 51, Page(s) 72–80

Abstract: The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural ... ...

Abstract	The first antibiotic, salvarsan, was deployed in 1910. In just over 100 years antibiotics have drastically changed modern medicine and extended the average human lifespan by 23 years. The discovery of penicillin in 1928 started the golden age of natural product antibiotic discovery that peaked in the mid-1950s. Since then, a gradual decline in antibiotic discovery and development and the evolution of drug resistance in many human pathogens has led to the current antimicrobial resistance crisis. Here we give an overview of the history of antibiotic discovery, the major classes of antibiotics and where they come from. We argue that the future of antibiotic discovery looks bright as new technologies such as genome mining and editing are deployed to discover new natural products with diverse bioactivities. We also report on the current state of antibiotic development, with 45 drugs currently going through the clinical trials pipeline, including several new classes with novel modes of action that are in phase 3 clinical trials. Overall, there are promising signs for antibiotic discovery, but changes in financial models are required to translate scientific advances into clinically approved antibiotics.
MeSH term(s)	Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/history ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacteria/genetics ; Bacteria/metabolism ; Bacterial Infections/drug therapy ; Bacterial Infections/microbiology ; Drug Discovery/history ; Drug Discovery/trends ; History, 20th Century ; History, 21st Century ; Humans
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2019-11-13
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1418474-6
ISSN	1879-0364 ; 1369-5274
ISSN (online)	1879-0364
ISSN	1369-5274
DOI	10.1016/j.mib.2019.10.008
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Article ; Online: Chemical warfare between fungus-growing ants and their pathogens.

Batey, Sibyl F D / Greco, Claudio / Hutchings, Matthew I / Wilkinson, Barrie

Current opinion in chemical biology

2020 Volume 59, Page(s) 172–181

Abstract: Fungus-growing attine ants are under constant threat from fungal pathogens such as the specialized mycoparasite Escovopsis, which uses combined physical and chemical attack strategies to prey on the fungal gardens of the ants. In defence, some species ... ...

Abstract	Fungus-growing attine ants are under constant threat from fungal pathogens such as the specialized mycoparasite Escovopsis, which uses combined physical and chemical attack strategies to prey on the fungal gardens of the ants. In defence, some species assemble protective microbiomes on their exoskeletons that contain antimicrobial-producing Actinobacteria. Underlying this network of mutualistic and antagonistic interactions are an array of chemical signals. Escovopsis weberi produces the shearinine terpene-indole alkaloids, which affect ant behaviour, diketopiperazines to combat defensive bacteria, and other small molecules that inhibit the fungal cultivar. Pseudonocardia and Streptomyces mutualist bacteria produce depsipeptide and polyene macrolide antifungals active against Escovopsis spp. The ant nest metabolome is further complicated by competition between defensive bacteria, which produce antibacterials active against even closely related species.
MeSH term(s)	Actinobacteria/physiology ; Animals ; Ants/microbiology ; Host-Pathogen Interactions ; Hypocreales/physiology ; Pseudonocardia/physiology ; Streptomyces/physiology ; Symbiosis
Language	English
Publishing date	2020-09-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2020.08.001
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Zs.A 4986: Show issues

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Article ; Online: Diet, Gut Microbes and Host Mate Choice: Understanding the significance of microbiome effects on host mate choice requires a case by case evaluation.

Leftwich, Philip T / Hutchings, Matthew I / Chapman, Tracey

BioEssays : news and reviews in molecular, cellular and developmental biology

2018 Volume 40, Issue 12, Page(s) e1800053

Abstract: All organisms live in close association with microbes. However, not all such associations are meaningful in an evolutionary context. Current debate concerns whether hosts and microbes are best described as communities of individuals or as holobionts ( ... ...

Abstract	All organisms live in close association with microbes. However, not all such associations are meaningful in an evolutionary context. Current debate concerns whether hosts and microbes are best described as communities of individuals or as holobionts (selective units of hosts plus their microbes). Recent reports that assortative mating of hosts by diet can be mediated by commensal gut microbes have attracted interest as a potential route to host reproductive isolation (RI). Here, the authors discuss logical problems with this line of argument. The authors briefly review how microbes can affect host mating preferences and evaluate recent findings from fruitflies. Endosymbionts can potentially influence host RI given stable and recurrent co-association of hosts and microbes over evolutionary time. However, observations of co-occurrence of microbes and hosts are ripe for misinterpretation and such associations will rarely represent a meaningful holobiont. A framework in which hosts and their microbes are independent evolutionary units provides the only satisfactory explanation for the observed range of effects and associations.
MeSH term(s)	Alleles ; Animals ; Biological Evolution ; Diet ; Drosophila melanogaster/physiology ; Female ; Gastrointestinal Microbiome/physiology ; Male ; Mating Preference, Animal/physiology ; Symbiosis ; Wolbachia/physiology
Language	English
Publishing date	2018-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.201800053
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Article ; Online: Cultivation of ammonia-oxidising archaea on solid medium.

Klein, Timothy / Poghosyan, Lianna / Barclay, J Elaine / Murrell, J Colin / Hutchings, Matthew I / Lehtovirta-Morley, Laura E

FEMS microbiology letters

2022 Volume 369, Issue 1

Abstract: Ammonia-oxidising archaea (AOA) are environmentally important microorganisms involved in the biogeochemical cycling of nitrogen. Routine cultivation of AOA is exclusively performed in liquid cultures and reports on their growth on solid medium are scarce. ...

Abstract	Ammonia-oxidising archaea (AOA) are environmentally important microorganisms involved in the biogeochemical cycling of nitrogen. Routine cultivation of AOA is exclusively performed in liquid cultures and reports on their growth on solid medium are scarce. The ability to grow AOA on solid medium would be beneficial for not only the purification of enrichment cultures but also for developing genetic tools. The aim of this study was to develop a reliable method for growing individual colonies from AOA cultures on solid medium. Three phylogenetically distinct AOA strains were tested: 'Candidatus Nitrosocosmicus franklandus C13', Nitrososphaera viennensis EN76 and 'Candidatus Nitrosotalea sinensis Nd2'. Of the gelling agents tested, agar and Bacto-agar severely inhibited growth of all three strains. In contrast, both 'Ca. N. franklandus C13' and N. viennensis EN76 tolerated Phytagel™ while the acidophilic 'Ca. N. sinensis Nd2' was completely inhibited. Based on these observations, we developed a Liquid-Solid (LS) method that involves immobilising cells in Phytagel™ and overlaying with liquid medium. This approach resulted in the development of visible distinct colonies from 'Ca. N. franklandus C13' and N. viennensis EN76 cultures and lays the groundwork for the genetic manipulation of this group of microorganisms.
MeSH term(s)	Agar ; Ammonia ; Archaea/genetics ; Culture Media ; Nitrification ; Oxidation-Reduction ; Phylogeny ; Soil Microbiology
Chemical Substances	Culture Media ; Ammonia (7664-41-7) ; Agar (9002-18-0)
Language	English
Publishing date	2022-03-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752343-9
ISSN	1574-6968 ; 0378-1097
ISSN (online)	1574-6968
ISSN	0378-1097
DOI	10.1093/femsle/fnac029
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Article: Dissolution of the Disparate: Co-ordinate Regulation in Antibiotic Biosynthesis.

McLean, Thomas C / Wilkinson, Barrie / Hutchings, Matthew I / Devine, Rebecca

Antibiotics (Basel, Switzerland)

2019 Volume 8, Issue 2

Abstract: Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, ... ...

Abstract	Discovering new antibiotics is vital to combat the growing threat of antimicrobial resistance. Most currently used antibiotics originate from the natural products of actinomycete bacteria, particularly
Language	English
Publishing date	2019-06-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2681345-2
ISSN	2079-6382
ISSN	2079-6382
DOI	10.3390/antibiotics8020083
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