Abstract
Visceral leishmaniasis (VL), mainly caused by the Leishmania donovani parasitic infection, constitutes a potentially fatal disease, for which treatment is primarily dependent on chemotherapy. The emergence of a resistant parasite towards current antileishmanial agents and increasing reports of relapses are the major concerns. Detailed research on the molecular interaction at the host-parasite interface may provide the identification of the parasite and the host-related factors operating during disease development. Genomic and proteomic studies highlighted several essential secretory and cytosolic proteins that play vital roles during Leishmania pathogenesis. The aim of this study was to identify membrane proteins from the Leishmania donovani parasite and the host macrophage that interact with each other using 2-DE/MALDI-TOF/MS. We identified membrane proteins including activated protein C kinase, peroxidoxin, small myristoylated protein 1 (SMP-1), and cytochrome C oxidase from the parasite, while identifying filamin A interacting protein 1(FILIP1) and β-actin from macrophages. We further investigated parasite replication and persistence within macrophages following the macrophage-amastigote model in the presence or absence of withaferin (WA), an inhibitor of activated C kinase. WA significantly reduced Leishmania donovani replication within host macrophages. This study sheds light on the important interacting proteins for parasite proliferation and virulence, and the establishment of infection within host cells, which can be targeted further to develop a strategy for chemotherapeutic intervention.
Highlights
The present study aims to identify Leishmania promastigote membrane proteins interacting with host macrophages using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry
The integrity of soluble and membrane protein fractions isolated from the THP-1 macrophage and L. donovani parasite was verified by SDS-PAGE
We identified a number of interacting membrane proteins involved in the Leishmania-macrophage interaction
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Visceral leishmaniasis (VL) is a potentially fatal protozoan infection caused by Leishmania donovani on the Indian subcontinent and L. infantum in the Mediterranean region. Internalization of parasites and their proliferation within the host cell are of primary concern to understand the key players involved in establishing infection and parasite persistence [1]. The genome of Leishmania shows constitutive expression in both flagellar and aflagellar forms. MRNA abundance does not correlate with the expression level of proteins in Leishmania [2]. Transcriptomic studies have provided a plethora of information regarding parasitic factors associated with drug resistance, parasite fitness, and the adaptive changes during different developmental stages of Leishmania [3]
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