Bioprospecting for novel antibiotics

Infectious diseases are a major threat to human health. Antibiotic resistance is large problem and superbugs have been found that are resistant to all antibiotics at hand. Estimates are that by 2050 more than 10 million people will die every year due to antimicrobial resistance if we do not act now. This project was aimed at identification of new antibiotics against pathogenic, multiresistant, Gram-negative bacteria. Fungi are well known to produce antibiotics. We have screened a collection of 10,207 strains of bacteria and found more than 200 strains that procued hits. Many antimicrobials were identified and it turned out that many of these are known antibiotics. To increase the diversity of secondary metabolites, we stimulated 1,030 strains pharmacologically to increase the repertoire of enzymes that produce secondary metabolites. This resulted in 25 strains that started to produce antimicrobials, some of which were known. Others were known secondary metabolites of which it was not known that they had antimicrobial activity. In parallel, we screened the library of fungi for compounds that inhibit bacterial quorum sensing, i.e. collaboration of bacteria at high density, which has a role in bacterial biofilm formation. We validated 39 hits and applied for a patent for the compound that was most promising for use in the clinic. All in all, this project has met its goals and produced the deliverables, most importantly several candidate antimicrobial and a quorum sensing inhibitor that may be developed further for use in the clinic.