The antimalarial drug quinine disrupts Tat2p-mediated tryptophan transport and causes tryptophan starvation.

ABSTRACT: Quinine is a major drug of choice for the treatment of malaria. However, the primary mode of quinine action is unclear, and its efficacy is marred by adverse reactions among patients. To help address these issues, a genome-wide screen for quinine sensitivity was carried out using the yeast deletion strain collection. Quinine-sensitive mutants identified in the screen included several that were defective for tryptophan biosynthesis (trp strains). This sensitivity was confirmed in independent assays and was suppressible with exogenous Trp, suggesting that quinine caused Trp starvation. Accordingly, quinine was found to inhibit [(3)H]Trp uptake by cells, and the quinine sensitivity of a trp1Delta mutant could be rescued by overexpression of Trp permeases, encoded by TAT1 and TAT2. The site of

SUBMITTER: Khozoie C 

PROVIDER: S-EPMC2709357 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature