Abstract
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).
Highlights
Whenever microorganisms share the same ecological niche – as, for example, soil fungi and soil bacteria – an orchestra of chemical compounds evolves reaching from mediators of stimulative symbiosis to detrimental antibiosis (Frey-Klett et al, 2011; Deveau et al, 2018)
A convenient high-throughput screening (HTS) assay to determine photo-activated minimal inhibitory concentrations (PhotoMIC) of pure compounds and extracts was established based on the EUCAST guideline
The light tolerance of the utilized model organisms (i.e., C. albicans, E. coli, and S. aureus) was tested and revealed that all microorganisms can cope with a light dose of H = 9.3 J/cm2 or even H = 30 J/cm2 of every tested wavelength
Summary
Whenever microorganisms share the same ecological niche – as, for example, soil fungi and soil bacteria – an orchestra of chemical compounds evolves reaching from mediators of stimulative symbiosis to detrimental antibiosis (Frey-Klett et al, 2011; Deveau et al, 2018). Plenty of such natural products have commercial values, especially as pharmaceuticals (Hyde et al, 2019). (Dresch et al, 2015; Basnet et al, 2017) These observations are rather the rule than the exception because for most basidiomycete genera, an antimicrobial activity was found in extracts from the fruiting bodies. We were wondering whether an important co-factor was missing in the common screening attempts
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