The Egon Stahl Award in Silver is awarded by GA Society to young scientists, who have published outstanding scientific work during the years following their graduation. Bianka Siewert, post doctoral researcher at the Center for Chemistry and Biomedicine of the University of Innsbruck, Austria, represents these preconditions in an ideal way, as she and her team, while studying Basidiomycetes fungi and the wide variety of pigments that give their fruiting bodies a colourful appearance, revealed a hidden function and new pharmaceutical opportunity of these pigments, photochemical defence: Activated by a ray of light, fungal pigments turn into powerful bullets destroying pathogens as well as malignant cancer cells.
Sunlight is not only a key factor in the primary metabolism of plants, but also a co-factor in light-activated plant defense. The principle is based on pigments that harvest the energy of photons and convert it into lethal signals. These pigments, known as photosensitizers, are either (i) natural precursors, (ii) present in plant tissues hidden from the sun, or (iii) synthesized on demand. In banana (Musa spp.), for example, the root turns reddish brown where it has been attacked by the predatory herbivore Radopholis similis. Once ingested by the nematode, this reddish-brown photosensitizer causes death as soon as the herbivore reaches the sunlight above. Thus, plants that cannot escape from predators have developed a successful defence strategy based on photochemistry.
But what about the second kingdom with “immobile” reproductive structures, the regnum fungi? Have fungi also developed photochemical defense strategies to protect their fruiting bodies? The work of Bianka Siewert addressed this question with two aims: (1) to discover new photo-activated drugs to combat human threats and (2) to explore new ecological roles of fungal pigments. By neatly combining different approaches from different scientific fields, evidence has already been provided in more than eleven peer-reviewed papers. Firstly, a set of screening assays were established for the discovery of photoactivity: A high-throughput screening assay based on a chemical probe was developed to detect photoactive extracts and guide isolation. A photoantimicrobial screening platform based on EUCAST and CLSI protocols was established. Finally, a state-of-the-art analytical method (FBMN) was fine-tuned to identify clusters of active molecules. These three assays were explicitly used to study fungal extracts, but their use is not limited to such, as they provide tools to discover natural photosensitizers from a variety of sources, including neglected ones such as lichens, marine organisms, or microbes.
Analytical studies were carried out to investigate the ecological function. The results support the hypothesis that photosensitizers protect reproduction of the fungi by accumulating in the gills. It was also shown that photoactivity is detrimental to a wide range of species: Adherent cells of human and mouse tissues are affected, as are bacteria and yeasts, and even invertebrates such as the larvae of Chaoborus spec..
Detailed molecular biological studies have shown that fungal photosensitizers have strong pharmaceutical potential. For example, 7,7′-biphyscion selectively induces apoptosis in the nanomolar range under blue light irradiation in cells of different cell lines, including the non-small cell lung cancer cell line A549. In addition, both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria were affected by treatment with light and fungal photosensitizers. Minimal inhibitory concentrations (MICs) in the range of established antibacterial agents were selectively achieved under irradiation.
In summary, her work shows that fungal photosensitizers do exist and that these natural products have a broad range of pharmacological activities, turning them into a lucrative starting point for future hit-to-lead approaches.