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Host cholesterol influences the activity of sterol biosynthesis inhibitors in Leishmania amazonensis.

Authors :
Andrade-Neto VV
Manso PPA
Pereira MG
de Cicco NNT
Atella GC
Pelajo-Machado M
Menna-Barreto RFS
Torres-Santos EC
Source :
Memorias do Instituto Oswaldo Cruz [Mem Inst Oswaldo Cruz] 2022 Apr 04; Vol. 117, pp. e220407. Date of Electronic Publication: 2022 Apr 04 (Print Publication: 2022).
Publication Year :
2022

Abstract

A significant percentage of exogenous cholesterol was found in promastigotes and amastigotes of all studied species of Leishmania, suggesting a biological role for this molecule. Previous studies have shown that promastigotes of Leishmania uptake more low-density lipoprotein (LDL) particles under pharmacological pressure and are more susceptible to ergosterol inhibition in the absence of exogenous sources of cholesterol. This work shows that the host's LDL is available to intracellular amastigotes and that the absence of exogenous cholesterol enhances the potency of sterol biosynthesis inhibitors in infected macrophages. A complete understanding of cholesterol transport to the parasitophorous vacuole can guide the development of a new drug class to be used in combination with sterol biosynthesis inhibitors for the treatment of leishmaniases.

Details

Language :
English
ISSN :
1678-8060
Volume :
117
Database :
MEDLINE
Journal :
Memorias do Instituto Oswaldo Cruz
Publication Type :
Academic Journal
Accession number :
35384972
Full Text :
https://doi.org/10.1590/0074-02760220407