Health Holland grant for bioprospecting fungi for novel antibiotics

Infectious diseases are treated effectively with antibiotics. However, resistance is emerging, which forms a major threat to human health. Antimicrobial resistance is recognized as a major problem and superbugs have been found that are resistant to all currently known antibiotics. It is estimated that if we do not act now, the number of antimicrobial resistance-associated deaths annually will rise from the already high number of 700 thousand in 2017 to more than 10 million in 2050.

The overall aim of this project is to identify novel antibiotics against pathogenic, multiresistant Gram-negative bacteria. Since the discovery of penicillin at the beginning of last century, fungi are well-known for the production of secondary metabolites with antibiotic activity. An initial screen of 10,000 strains of fungi from the Westerdijk Fungal Biodiversity Institute for production of compounds with antibiotic activity yielded close to 200 positive hits. To increase the repertoire of secondary metabolites, expressed by fungi, silent gene clusters will be activated pharmacologically in 1,000 strains of fungi, which is likely to yield additional positive hits with antibiotic activity. This project aims to isolate and identify compounds with antibiotic activity. Minimal inhibitory concentration values and maximal tolerable doses of the purified compounds will be determined. Finally, the antibiotics will be subjected to a range of molecular-genetic and cytological analyses to obtain insight into the working mechanism of the newly identified antibiotics.

Antibiotics with distinct working mechanisms compared to the antibiotics that are currently being used in the clinic, will be selected for further development. These lead compounds have the potential to be rapidly developed further for use in the clinic.

Prof. dr. Jeroen den Hertogis group leader and deputy director research at the Hubrecht Institute (KNAW) in Utrecht and professor of Molecular Developmental Zoology at Leiden University. His group studies the function of protein-tyrosine phosphatases in vertebrate development, using zebrafish embryos as a model. His group is also searching for novel bioactive molecules produced by fungi from the Westerdijk Fungal Biodiversity Institute.