Pseudomonas aeruginosa is an opportunistic bacterium that causes severe nosocomial infections and chronic infections in cystic fibrosis patients. This pathogenic bacterium is often called a "superbug" due to its ability to develop resistance mechanisms against almost all available antibiotics in clinical use. With the increasing lack of therapeutic options, the effective treatment of patients becomes more and more difficult. To overcome this resistance problem, new targets for pharmaceuticals are required. Such a potential target is PhzF, a key protein involved in the biosynthesis of phenazines, which can act as important virulence factors. Other
PhzF-like isomerases are often involved in essential metabolic pathways, such as lysine biosynthesis, energy or proline metabolism. Hence, the PhzF-like isomerases state putative drug targets as well. The human genome also encodes for PhzF-like isomerases, which seem to be involved in diabetes and cancer. For both, P. aeruginosa and Homo sapiens, the majority of these proteins is not characterized yet or just rarely explored in general.
In this project, we want to confirm and associate specific functions for the PhzF-like isomerases from
P. aeruginosa and Homo sapiens. Therefore, recombinant proteins are produced in E. coli cells and purified with different chromatographic techniques. The purified proteins are used for crystallographic and enzymatic experiments. Furthermore, metabolic analysis is carried out in cooperation with the research group of Prof. Brönstrup to elucidate the function of uncharacterized PhzF-like isomerases.
For PhzF itself, putative inhibitors are tested and crystallized in close collaboration with the research group of Prof. Kunick.
Name of Doctoral Researcher
Philipp Schneider
Name of Supervisor
Wulf Blankenfeldt
Institute / Department
Department Structure and Function of Proteins, Helmholtz Centre for Infection Research, Braunschweig
Contact details
philipp.schneider@helmholtz-hzi.de