A domino effect in drug action: From metabolic assault towards parasite differentiation. Trypanosoma brucei

Glycolysis is the sole free-energy source for the deadly parasite Trypanosoma brucei and is therefore a possible target pathway for anti-trypanosomal drugs. Plasma-membrane glucose transport exerts high control over trypanosome glycolysis and hence the transporter is a promising drug target. Here we show that at high inhibitor concentrations, inhibition of trypanosome glucose transport causes cell death. Most interestingly, sublethal concentrations initiate a domino effect in which network adaptations enhance inhibition. Overall design: total of 5 slides, including 3 biological replicates and dyeswap