Glutamine metabolism modulates azole susceptibility in Trypanosoma cruzi amastigotes.

ABSTRACT: The mechanisms underlying resistance of the Chagas disease parasite, Trypanosoma cruzi, to current therapies are not well understood, including the role of metabolic heterogeneity. We found that limiting exogenous glutamine protects actively dividing amastigotes from ergosterol biosynthesis inhibitors (azoles), independent of parasite growth rate. The antiparasitic properties of azoles are derived from inhibition of lanosterol 14α-demethylase (CYP51) in the endogenous sterol synthesis pathway. We find that carbons from ¹³C-glutamine feed into amastigote sterols and into metabolic intermediates that accumulate upon CYP51 inhibition. Incorporation of ¹³C-glutamine into endogenously synthesized sterols is increased with BPTES treatment, an inhibitor of host glutam

SUBMITTER: Dumoulin PC 

PROVIDER: S-EPMC7707839 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature