Molecular Mechanisms of Drug Resistance in Spp

Overview

Journal Pathogens

Date 2024 Oct 25

PMID 39452707

Authors

Maria Juliana Moncada-Diaz

Cristian Camilo Rodriguez-Almonacid

Eyson Quiceno-Giraldo

Francis T H Khuong

Carlos Muskus

Zemfira N Karamysheva

Affiliations

Soon will be listed here.

Abstract

The protozoan parasite causes leishmaniasis, a neglected tropical disease, that disproportionately affects underdeveloped countries. This disease has major health, economic, and social implications, particularly because of the limited treatment options, high cost, the severe side effects associated with available therapeutics, and the high rate of treatment failure caused by the parasites' growing resistance to current medications. In this review, we describe first the common strategies used by pathogens to develop drug resistance and then focus on the arsenal of available drugs to treat leishmaniasis, their modes of action, and the molecular mechanisms contributing to drug resistance in spp., including the role of genomic, transcriptional, and translational control. We focus more specifically on our recent discovery of translational reprogramming as a major driver of drug resistance leading to coordinated changes in the translation of transcripts and orchestrating changes in metabolome and lipidome to support drug resistance. A thorough understanding of these mechanisms is essential to identify the key elements needed to combat resistance and improve leishmaniasis treatment methods.

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