Microbial Production of Photosensitizers

The production of antibiotics by fungi was discovered by chance almost 100 years ago. With the help of targeted development and technical excellence, it was possible to synthesize penicillin on a large- scale using microbes. This has saved millions of lives. However, in recent years the WHO has been sounding the alarm about the rise of multi-resistant bacteria; the tried and tested antibiotics are ineffective here. To avert the impending health catastrophe, there is a need for action at various levels, for example in the search for new treatment strategies. These are necessary to use so-called reserve antibiotics as sparingly and prudently as possible. PenTaPho focuses on the discovery and production of active substances for such a novel treatment strategy. Specifically, the PenTaPho project focuses on antimicrobial photodynamic therapy (aPDT), also known as photodynamic inhibition (PDI). This involves combining an active ingredient with light to produce a local antimicrobial effect. Various global studies have shown the high potential of this treatment strategy, for example in the treatment of periodontitis or diabetic foot. However, the number of suitable clinical drug candidates is small. In the predecessor project PhotoFungal (FWF, P31915), promising new drug candidates were isolated from fungi. However, the producers were so-called ectomycorrhiza fungi, which could only be collected seasonally. To counteract this disadvantage, the PenTaPho project is concentrating on the production of so-called photosensitizers from molds, like the penicillin-producing strain Penicillium chrysogenum. Various species of the genera Penicillium and Talaromyces were selected based on literature research and preliminary tests. As part of the project, multiple strains of these species will be cultivated under different conditions and their extracts tested to investigate the most promising candidates and their ingredients in detail. After small-scale cultivation on Petri dishes, further cultivation experiments will be carried out with the best strains to move from so-called solid-phase cultivation to cultivation in bioreactors. In addition, various photopharmaceutical tests will be carried out to determine the photoantimicrobial potential in detail and against multi-resistant pathogens. The photocytotoxic potential is also evaluated to select candidates that do not damage the surrounding tissue as much as possible.