Förderung BE 2546/1-1im Rahmen des DFG-Schwerpunktprogramms 1316 „Wirtsadaptierter Metabolismus von bakteriellen Infektionserregern“
K. Becker
09/2008 – 08/2011
Staphylococcus aureus small-colony variants (SCVs) represent a phenotypic subpopulation typically associated with chronic and persistent infections. These variants seem to be specifically adapted for an intracellular life style. Using site-directed mutants in hemin and menadione biosynthesis mimicking the phenotype of clinically derived hemin- and menadione-auxotrophic SCVs, first insights into the SCV physiology were previously gained by transcriptomic, proteomic, and metabolomic approaches. However, the metabolism of clinically derived SCVs is still unstudied. Here, the dynamic metabolic changes caused by the bidirectional phenotypic switch between the normal and the SCV phenotype will be investigated with special regard to the adaption of the SCV phenotype on the intracellular host cell milieu. For this purpose, the provoked phenotype switch will be traced by Fourier-transform infrared spectroscopy and the pathogen’s intracellular adaption will be analyzed by bioanalytical and systemsbiological approaches. In parallel, the host cell response on invasion and persistence by S. aureus will be analyzed. Finally, a controlled switch of the S. aureus phenotype by the application of electron transport-influencing compounds will be studied to open up alternative ways for the therapy of acute and chronic S. aureus infections.
