Mark Brönstrup studied Chemistry at the Philipps-Universität Marburg and at the Imperial College in London. In 1999 he received his doctorate from the Technical University Berlin in Organic Chemistry. After his graduation, he worked from 2000 to 2013 for Aventis, Sanofi-Aventis and Sanofi, complemented by a research sabbatical in 2003 at Harvard Medical School. There, he led the Natural Product Sciences with the goal of discovering leads from natural sources and optimising them to clinical candidates, and he dealt with translational research projects as a section head for Biomarkers & Diagnostics in the Diabetes Division, and a domain head for Biomarkers, Bioimaging & Biological Assays at Sanofi. Since December 2013, he heads the department Chemical Biology at the Helmholtz Centre for Infection Research. Additionally, he holds a Professorship (W3) at the Leibniz Universität Hannover. His research is focused on the discovery and the characterization of novel antibacterial and antiviral drugs.
Assault, Siege or Trojan Horse Strategy: Use of Natural Products to Fight Bacterial Infections
Multidrug resistant bacterial pathogens have become a major health concern. Especially infections by gram-negative bacteria are challenging, since their complex cell membrane architecture strongly impedes the uptake of drugs. Because microbial natural products continue to be the prime source to tackle these issues, we have investigated natural products as the basis for novel antibiotic.
A broad spectrum of gram-positive and gram-negative pathogens is addressed by cystobactamids, oligo-arylamids originally isolated from Cystobacter sp.. Our efforts to optimize the antibiotic properties of the cystobactamids by medicinal chemistry will be presented.
Beyond a classic ‘assault’ of bacteria with such antibiotics, the conjugation of natural products to targeting functions has been beneficial to improve their drug properties. In the so-called Trojan Horse Strategy, antibiotics are conjugated to siderophores to hijack the bacterial siderophore transport system, and thereby enhance the intracellular accumulation of drugs. We synthesized novel artificial siderophores, characterized their transport and resistance mechanisms, and their efficacy when coupled to antibiotic natural products. Finally, we present a novel approach for the selective bacterial targeting and infection-triggered release of antibiotic conjugates in the alternative siege concept, using the lipopeptide colistin as the antibiotic effector.
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