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Metabolism of Microbial Pathogens

Martin Blume

Life-long persistence of pathogen subpopulations is a hallmark of many zoonotic infections with bacterial, fungal and parasitic pathogens. Our research aims to provide a metabolomics platform for accelerated development of new chemotherapies against zoonotic infections. Further, we develop an imaging based platform to study physiology on single cell level that should aid characterization of small and complex pathogen subpopulations and inform future research strategies for other persisting zoonotic infections. As proof-of-concept we target chronic T. gondii infections with the goal to interrupt foodborne transmission. Toxoplasma gondii is an Apicomplexan parasite that infects virtually all warm-blooded animals and causes life-long infections in up to 30% of humans globally and >50% in Germany. Chronically persisting parasite tissue cysts, termed bradyzoites, are key for transmission via undercooked meat products and remission, but cannot be targeted by available chemotherapies.

The junior group analyses the metabolic signatures of T. gondii bradyzoites for the evidence-based development of novel chemotherapies. These studies will include systematic screening of antiprotozoal compound libraries using a metabolomic approach based on liquid and gas chromatography-coupled mass spectrometry. Identification and reverse-genetic confirmation of molecular targets will facilitate development and optimization of antiprotozoal compounds into much needed drug candidates.

In a complementary approach the group studies the physiological basis of persistence in veterinary and clinical parasite isolates. Clonal T. gondii tissue cysts are phenotypically highly heterogeneous. We are establishing fluorescent parasite reporter cell lines to monitor key physiological parameters and cell divisions during stress responses at single cell resolution. The obtained data will be used to calibrate a computational model that allows us to identify the contribution of phenotypic heterogeneity to the persistence of T. gondii.

Please contact Martin Blume for further information about both projects and associated PhD positions.

Date: 28.07.2017