This project prepares the preclinical development of the semi-synthetic chlorotonil derivative dehalogenil for the treatment of bacterial infections caused by Gram-positive pathogens. Dehalogenil impresses with its potent and very rapid antibacterial effect, which is triggered by membrane depolarization and potassium efflux. Further studies on the mechanism of action have revealed [...]

Pseudomonas aeruginosa is a hospital-acquired pathogen that causes difficult-to-treat infections, especially when caused by antibiotic-resistant isolates. There is a high unmet medical need, particularly for pneumonia, which often progresses to severe disease with high morbidity and mortality despite adequate antibiotic treatment. In order to increase the translational reach of the [...]

Gram-negative bacteria are naturally insensitive to many antibiotics due to their additional outer membrane. In addition, the bacteria have acquired resistance to clinically used antibiotics in recent decades, resulting in multidrug-resistant bacteria. Novel classes of antibiotics are needed to counteract these existing resistance mechanisms. However, no new antibiotic class against [...]

In the current WHO list of bacterial priority pathogens (WHO BPPL 2024), the World Health Organisation classifies carbapenem-resistant Pseudomonas aeruginosa bacteria as a high-priority pathogen, which means there is an urgent need for new anti-infectives to combat this problematic bacterium. To address this need, the PAFAP project has brought together a [...]

The challenge of antibiotic drug development today is the discovery and optimisation of novel bioactive compounds that do not show cross-resistances with clinically applied antibiotics, ideally due to a novel mode of action (MoA) which adresses unexploited microbial targets. In the case of chelocardin, this antibiotic substance was identified several [...]