Exploitation of vitamin B1 as pro-drug in Malaria and MRSA

• Grant number: 18/00562-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2018
• End date: April 30, 2019
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Carsten Wrenger
• Grantee: Larissa Prechedes de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/26722-8 - Drug discovery against human infectious diseases, AP.TEM

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 pro-drug discovery by exploiting the vitamin B1 biosynthetic pathway of the human pathogens Plasmodium falciparum, the parasite responsible for predominate cases of severe malaria, and the multi-resistant bacteria Staphylococcus aureus MRSA. Pro-drugs will be analyzed against the recombinantly expressed plasmodial and MRSA thiamine pyrophosphokinase (TPK) for their substrate acceptability as well as for their druggability at the cellular level using a respective transgenically modified P. falciparum cell line. (AU)