David and Goliath: chemical perturbation of eukaryotes by bacteria

Ho, Louis; Nodwell, Justin R.

doi:10.1007/s10295-015-1686-6

Cited by 6 publications

(7 citation statements)

References 196 publications

(193 reference statements)

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“…These screens should harness more than just live/dead screening. In other words, we should look for interesting developmental and behavioural phenotypes using well-developed model systems” ( Ho and Nodwell, 2016 ). The screen described here aptly fits the above description; we have successfully screened strains producing putative anti-fungal natural products, from a major collection of actinomycete bacteria, for their ability to induce cell shape defects in S. pombe , with the aim of identifying chemical entities capable of exerting effects on the cell cycle/cell morphology.…”

Section: Discussionmentioning

confidence: 99%

“…Actinomycetes are well known for synthesising natural products, for example, bleomycin ( Umenzawa et al, 1966 ) and adriamycin ( Arcamone et al, 1969 ), with anti-eukaryotic cell activities. The rationale behind this approach was that as the mechanisms that determine cell morphology and cell cycle in prokaryotic and eukaryotic organisms are different, and as soil-dwelling bacteria may be competing in the same ecological niche as fungi, these eukaryotic-specific processes could be targets for bacterially synthesised secondary metabolites ( Ho and Nodwell, 2016 ). Thus, evolution would have naturally selected for prokaryotes able to produce antifungal agents, and thus may provide a richer source of ‘hits’ than would be obtained from a library of randomly synthesised molecules.…”

Section: Introductionmentioning

confidence: 99%

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Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast

Lewis

Allenby

et al. 2017

Journal of Cell Science

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This study was designed to identify bioactive compounds that alter the cellular shape of the fission yeast Schizosaccharomyces pombe by affecting functions involved in the cell cycle or cell morphogenesis. We used a multidrug-sensitive fission yeast strain, SAK950 to screen a library of 657 actinomycete bacteria and identified 242 strains that induced eight different major shape phenotypes in S. pombe. These include the typical cell cycle-related phenotype of elongated cells, and the cell morphology-related phenotype of rounded cells. As a proof of principle, we purified four of these activities, one of which is a novel compound and three that are previously known compounds, leptomycin B, streptonigrin and cycloheximide. In this study, we have also shown novel effects for two of these compounds, leptomycin B and cycloheximide. The identification of these four compounds and the explanation of the S. pombe phenotypes in terms of their known, or predicted bioactivities, confirm the effectiveness of this approach.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast

Lewis

Allenby

et al. 2017

Journal of Cell Science

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“…2-MIB biosynthetic gene clusters were identi ed in other strains by using BLAST for the 2-MIB terpene synthase gene. Identifying strains that encode both 2-MIB and a possible insect toxin was carried out by querying combined terpene synthase of 2-MIB and core genes encoding compounds that would potentially be broadly toxic to higher eukaryotes (14).…”

Section: Bioinformaticsmentioning

confidence: 99%

“…Others, such as the DNA intercalating agents daunorubicin, actinomycin and cosmomycin, can serve as a defense mechanism against bacteriophage infection (13). A smaller number of these compounds are active against eukaryotic cells and some of these are used as anticancer drugs, immune suppressants and anthelminthic drugs (14).…”

Section: Introductionmentioning

confidence: 99%

Chemical entrapment and killing of insects by bacteria

Daniel-Ivad

Jeedigunta

et al. 2020

Preprint

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Actinobacteria such as the filamentous streptomycetes are widely known for their ability to produce specialized metabolites that include antibacterial and antifungal compounds. In addition, a growing body of work demonstrates that many insects harbour actinobacteria on their bodies and in their nests. The result of these mutualistic relationships is the protection of their offspring or food sources by virtue of the bacterially encoded specialized metabolites. However, some actinobacteria produce molecules that are toxic to insects and the relevance of this toxicity in nature is unknown. We have explored interactions between streptomycetes and the fruit fly Drosophila. We find that many streptomycetes produce specialized metabolites that have potent larvicidal effects against the fly. Larvae that ingest spores of the species that produce these toxic molecules die as a result. Strikingly, the mechanism of toxicity is specific to the bacterium’s chemical arsenal: cosmomycin D producing cells induce a relatively slow-acting cell death-like response in the larval digestive tract and avermectin producing cells induce rapid onset, whole-body paralysis. We further show that fruit flies are attracted to the volatile terpene 2-methylisoborneol that is produced by most streptomycetes. This interaction can influence their food choice and egg-laying destination such that they preferentially deposit their eggs on contaminated food sources. As a result, the larvae that hatch in these toxic environments are subsequently killed. This phenomena of terpene-mediated attraction and specialized metabolite toxicity must pose a significant risk to insects in nature.

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“…Others, such as the DNA-intercalating agents daunorubicin, actinomycin and cosmomycin, can serve as a defence mechanism against bacteriophage infection 13 . A smaller number of these compounds are active against eukaryotic cells and some of these are used as anticancer drugs, immune suppressants and anthelminthic drugs 14 .…”

mentioning

confidence: 99%

Chemical entrapment and killing of insects by bacteria

Daniel-Ivad

Jeedigunta

et al. 2020

Nat Commun

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Actinobacteria produce antibacterial and antifungal specialized metabolites. Many insects harbour actinobacteria on their bodies or in their nests and use these metabolites for protection. However, some actinobacteria produce metabolites that are toxic to insects and the evolutionary relevance of this toxicity is unknown. Here we explore chemical interactions between streptomycetes and the fruit fly Drosophila melanogaster. We find that many streptomycetes produce specialized metabolites that have potent larvicidal effects against the fly; larvae that ingest spores of these species die. The mechanism of toxicity is specific to the bacterium’s chemical arsenal: cosmomycin D producing bacteria induce a cell death-like response in the larval digestive tract; avermectin producing bacteria induce paralysis. Furthermore, low concentrations of volatile terpenes like 2-methylisoborneol that are produced by streptomycetes attract fruit flies such that they preferentially deposit their eggs on contaminated food sources. The resulting larvae are killed during growth and development. The phenomenon of volatile-mediated attraction and specialized metabolite toxicity suggests that some streptomycetes pose an evolutionary risk to insects in nature.

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David and Goliath: chemical perturbation of eukaryotes by bacteria

Cited by 6 publications

References 196 publications

Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast

Screening and purification of natural products from actinomycetes that affect the cell shape of fission yeast

Chemical entrapment and killing of insects by bacteria

Chemical entrapment and killing of insects by bacteria

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