| Autor: |
Voyton CM; Department of Chemistry and Biochemistry , Brigham Young University , Provo , Utah 84601 , United States., Morris MT, Ackroyd PC; Department of Chemistry and Biochemistry , Brigham Young University , Provo , Utah 84601 , United States., Morris JC, Christensen KA; Department of Chemistry and Biochemistry , Brigham Young University , Provo , Utah 84601 , United States. |
| Jazyk: |
angličtina |
| Zdroj: |
ACS infectious diseases [ACS Infect Dis] 2018 Jul 13; Vol. 4 (7), pp. 1058-1066. Date of Electronic Publication: 2018 May 14. |
| DOI: |
10.1021/acsinfecdis.8b00058 |
| Abstrakt: |
Trypanosoma brucei, which causes human African typanosomiasis (HAT), derives cellular ATP from glucose metabolism while in the mammalian host. Targeting glucose uptake or regulation in the parasite has been proposed as a potential therapeutic strategy. However, few methods have been described to identify and characterize potential inhibitors of glucose uptake and regulation. Here, we report development of a screening assay that identifies small molecule disrupters of glucose levels in the cytosol and glycosomes. Using an endogenously expressed fluorescent protein glucose sensor expressed in cytosol or glycosomes, we monitored intracellular glucose depletion in the different cellular compartments. Two glucose level disrupters were identified, one of which only exhibited inhibition of glycosomal glucose and did not affect cytosolic levels. In addition to inhibiting glucose uptake with relatively high potency (EC 50 = 700 nM), the compound also showed modest bloodstream form parasite killing activity. Expanding this assay will allow for identification of candidate compounds that disrupt parasite glucose metabolism. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
