Does the chemistry of fungal pigments demand the existence of photoactivated defense strategies in basidiomycetes?

Siewert, Bianka

doi:10.1007/s43630-021-00034-w

Cited by 16 publications

(20 citation statements)

References 137 publications

(172 reference statements)

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“…As part of a putative light-activated defense system, the first photosensitizers, i.e., light-activated chemical compounds, were recently activity-guided discovered in fruiting bodies of macromycota ( Hammerle, 2021 ). Light-activated antimicrobial effects of basidiomycetes are, however, not described yet, despite promising hints ( Siewert, 2021 ). The lack of described photoantimicrobials might be the consequence of a non-existing photo-antimicrobial high-throughput screening (HTS) assay.…”

Section: Introductionmentioning

confidence: 99%

A New High-Throughput-Screening-Assay for Photoantimicrobials Based on EUCAST Revealed Unknown Photoantimicrobials in Cortinariaceae

et al. 2021

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Antimicrobial resistance is one of the biggest health and subsequent economic threat humanity faces. Next to massive global awareness campaigns, governments and NGOs alike stress the need for new innovative strategies to treat microbial infections. One of such innovative strategies is the photodynamic antimicrobial chemotherapy (PACT) in which the synergistic effects of photons and drugs are exploited. While many promising reports are available, PACT – and especially the drug-design part behind – is still in its infancy. Common best-practice rules, such as the EUCAST or CLSI protocols for classic antibiotics as well as high-throughput screenings, are missing, and this, in turn, hampers the identification of hit structures. Hit-like structures might come from synthetic approaches or from natural sources. They are identified via activity-guided synthesis or isolation strategies. As source for new antimicrobials, fungi are highly ranked. They share the same ecological niche with many other microbes and consequently established chemical strategies to combat with the others. Recently, in members of the Cortinariaceae, especially of the subgenus Dermocybe, photoactive metabolites were detected. To study their putative photoantimicrobial effect, a photoantimicrobial high-throughput screening (HTS) based on The European Committee on Antimicrobial Susceptibility Testing (EUCAST) was established. After validation, the established HTS was used to evaluate a sample set containing six colorful representatives from the genus Cortinarius (i.e., Cortinarius callisteus, C. rufo-olivaceus, C. traganus, C. trivialis, C. venetus, and C. xanthophyllus). The assay is built on a uniform, light-emitting diode (LED)-based light irradiation across a 96-well microtiter plate, which was achieved by a pioneering arrangement of the LEDs. The validation of the assay was accomplished with well-known photoactive drugs, so-called photosensitizers, utilizing six distinct emission wavelengths (λexc = 428, 478, 523, 598, or 640 nm) and three microbial strains (Candida albicans, Staphylococcus aureus, and Escherichia coli). Evaluating the extracts of six Cortinarius species revealed two highly promising species, i.e., C. rufo-olivaceus and C. xanthophyllus. Extracts from the latter were photoactive against the Gram-positive S. aureus (c = 7.5 μg/ml, H = 30 J/cm2, λ = 478 nm) and the fungus C. albicans (c = 75 μg/ml, H = 30 J/cm2, λ = 478 nm).

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Section: Introductionmentioning

confidence: 99%

A New High-Throughput-Screening-Assay for Photoantimicrobials Based on EUCAST Revealed Unknown Photoantimicrobials in Cortinariaceae

et al. 2021

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“…Looking with a photochemist's eye at the structure of these fungal AQs 4 , however, an additional potential pharmacological application can be suggested: Photodynamic therapy (PDT) 5 . PDT as a treatment strategy utilizes the synergistic effect of the light and the drug, the so-called photosensitizer (PS).…”

Section: Introductionmentioning

confidence: 99%

Targeted isolation of photoactive pigments from mushrooms yielded a highly potent new photosensitizer: 7,7′-biphyscion

Hammerle

Bingger

Pannwitz

et al. 2022

Sci Rep

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Pigments of fungi are a fertile ground of inspiration: they spread across various chemical backbones, absorption ranges, and bioactivities. However, basidiomycetes with strikingly colored fruiting bodies have never been explored as agents for photodynamic therapy (PDT), even though known photoactive compound classes (e.g., anthraquinones or alkaloids) are used as chemotaxonomic markers. In this study, we tested the hypothesis that the dyes of skin-heads (dermocyboid Cortinarii) can produce singlet oxygen under irradiation and thus are natural photosensitizers. Three photosensitizers based on anthraquinone structures were isolated and photopharmaceutical tests were conducted. For one of the three, i.e., (–)-7,7′-biphyscion (1), a promising photoyield and photocytotoxicity of EC50 = 0.064 µM against cancer cells (A549) was found under blue light irradiation (λexc = 468 nm, 9.3 J/cm2). The results of molecular biological methods, e.g., a viability assay and a cell cycle analysis, demonstrated the harmlessness of 1 in the dark and highlighted the apoptosis-inducing PDT potential under blue light irradiation. These results demonstrate for the first time that pigments of dermocyboid Cortinarii possess a so far undescribed activity, i.e., photoactivity, with significant potential for the field of PDT. The dimeric anthraquinone (–)-7,7′-biphyscion (1) was identified as a promising natural photosensitizer.

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“…Agaricoid fungi of the genus Cortinarius subgenus Dermocybe often have conspicuously colored fruiting bodies with auburn, orange, or even greenish-yellow hues, which owe their striking appearance to the presence of anthraquinone (AQ) pigments [1]. After being used as fabric dyes in the 20th century [2], a previously overlooked bioactivity-i.e., photoactivity [3]-has brought these metabolites back into the spotlight. A dimeric AQ isolated from the marsh webcap (Cortinarius uliginosus) was shown to induce blue light-dependent cell death in various cancer cell lines in Article Related Abbreviations: AQ, anthraquinone; CPC, centrifugal partition chromatography; DMSO, dimethyl sulfoxide; LP, lower phase; MeOH, methanol; MLLP, multiple liquid-liquid partition; PT, pigmentation type; SI, electronic supplementary information; UP, upper phase the nanomolar range while being inactive in the absence of light [4].…”

Section: Introductionmentioning

confidence: 99%

A convenient separation strategy for fungal anthraquinones by centrifugal partition chromatography

Hammerle

Zwerger

Höck

et al. 2022

J of Separation Science

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As recently shown, some fungal pigments exhibit significant photoactivity turning them into promising agents for the photodynamic treatment of microbial infections or malignant diseases. In the present study, a separation strategy for fungal anthraquinones was developed based on centrifugal partition chromatography. A suitable method was explored employing a methanolic extract of the fruiting bodies of Cortinarius sanguineus (Agaricales, Basidiomycota). An excellent fractionation was achieved using a biphasic solvent system comprising chloroform/ethyl acetate/methanol/water/acetic acid (3:1:3:2:1, v/v/v/v/v) operating in ascending mode. Experiments on an analytical scale with extracts of closely related Cortinarius species exhibited broad applicability of the devised system. Up to six pigments could be purified directly from the crude extract. Preparative‐scale fractionation of the methanol extracts of C. malicorius and C. sanguineus demonstrated that up‐scaling was possible without compromising selectivity.

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Does the chemistry of fungal pigments demand the existence of photoactivated defense strategies in basidiomycetes?

Cited by 16 publications

References 137 publications

A New High-Throughput-Screening-Assay for Photoantimicrobials Based on EUCAST Revealed Unknown Photoantimicrobials in Cortinariaceae

A New High-Throughput-Screening-Assay for Photoantimicrobials Based on EUCAST Revealed Unknown Photoantimicrobials in Cortinariaceae

Targeted isolation of photoactive pigments from mushrooms yielded a highly potent new photosensitizer: 7,7′-biphyscion

A convenient separation strategy for fungal anthraquinones by centrifugal partition chromatography

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