Integrative Biology

Biography

Biography: Mark Bronstrup

Abstract

Our efforts to generate novel antibacterial and antiviral lead substances through chemical biology methods will be highlighted through two projects. Infections caused by pathogenic bacteria represent a major health threat that is expected to rise further in the future. The need for novel antibiotics is currently not met by R&D efforts, in particular in the area of infections caused by Gram-negative bacteria. A main scientific hurdle is the lack of understanding how to assure a sufficient translocation of bioactive molecules across the Gram-negative cell wall. In the talk, our efforts to induce an active transport of small molecules into Gram negative bacteria and methods to quantify such uptake will be presented. We report a series of theranostics agents based on DOTAM derivatives comprising siderophores that actively target bacteria, inhibit bacterial growth and demonstrate efficacy to visualize bacterial infections in mice by optical imaging in vivo. In addition, two orthogonal approaches to quantify the intracellular accumulation of such conjugates will be presented. In the second part of the talk, two antiviral natural products with broad-spectrum action against multiple human pathogenic viruses will be presented. Broad spectrum antiviral agents have the potential to improve health-care of infected individuals including patients infected with emerging viruses against which no directly acting antiviral drug is yet available, patients co-infected with two or more viruses and patients infected with viruses that have developed resistance to standard antiviral treatment. Both lead compounds interfere with extra and intracellular lipid metabolism pathways utilized by different viruses.