EMU 2015/26722-8 CLARIOstar microplate reader

Abstract

Infectious diseases are a threat to mankind and currently the causative pathogens are spreading geographically due to globalisation and developing drug resistance. Current resistance to chemotherapeutics is occurring to almost all pathogens and therefore new drug targets and/or novel modi of drug target efficacy is urgently needed. In this grant application the focus will be drawn on suicide drug discovery by exploiting the vitamin B1/B6 biosynthetic pathways of the human pathogens Plasmodium falciparum, the parasite responsible for predominate cases of severe malaria, and the multi-resistant bacteria Staphylococcus aureus MRSA. Compounds will be identified and designed for incorporation into pathogens' metabolism after crystal structure evaluation of the respective vitamin B1/B6 biosynthetic enzymes. Thereby the new compounds are intended to poison the respective vitamin-dependent enzyme. Counter selection will be performed against human cells as well as transgenically modified human cells which are expressing nuclear receptors for xenobiotic sensing as reporter gene chimeras. (AU)