Fabian Grein's research group is investigating new targets for antibiotics against staphylococci. Staphylococcus aureus causes a broad range of infections, in particular soft tissue, bone and skin infections, but also bloodstream infections and very often postoperative wound infections. Since this pathogen has special abilities to quickly develop spontaneous or acquired resistance to almost all antibiotics, the development of novel drugs is urgently needed. The DZIF junior research group "Anti-staphylococcal targets" is therefore engaged in the identification and validation of target structures in S. aureus whose blocking allows specific killing of the pathogen or leads to an increase or restoration of sensitivity towards classical antibiotics.
One focus of the research group is on target structures that are involved in cell wall biosynthesis and the modification of the cell envelope. Blocking these targets can either lead directly to cell death or restore the efficacy of classical cell wall biosynthesis inhibitors. The researchers are specifically looking for substances that can resensitize resistant staphylococcal strains to ß-lactam antibiotics (for example penicillins) or daptomycin.
For example, the scientists established specific assays to identify inhibitors of enzymes of the D-alanine metabolism in S. aureus. D-alanine is an essential building block of the staphylococcal cell wall and the enzymes of the metabolism are therefore important or fundamental for the growth and virulence of S. aureus. They lack human homologues and are therefore attractive as targets for the discovery of highly selective antibiotics. The screening technologies are developed in high-throughput formats and are used to screen compound and extract libraries for inhibitors.