Contribution of proteomics of Leishmania spp. to the understanding of differentiation, drug resistance mechanisms, vaccine and drug development

Abstract

:Leishmania spp., protozoan parasites with a digenetic life cycle, cause a spectrum of diseases in humans. Recently several Leishmania spp. have been sequenced which significantly boosted the number and quality of proteomic studies conducted. Here a historic review will summarize work of the pre-genomic era and then focus on studies after genome information became available. Firstly works comparing the different life cycle stages, in order to identify stage specific proteins, will be discussed. Identifying of post-translational modifications by proteomics especially phosphorylation events will be discussed. Further the contribution of proteomics to the understanding of the molecular mechanism of drug resistance and the investigation of immunogenic proteins for the identification of vaccine candidates will be summarized. Approaches of how potentially secreted proteins were identified are discussed. So far 30 -35% of the total predicted proteome of Leishmania spp. has been identified. This comprises mainly the abundant proteins, therefore the last section will look into technological approaches how this coverage may be increased and what the gel-free and gel-based proteomics have to offer will be compared.

Multi-analytical platform metabolomic approach to study miltefosine mechanism of action and resistance in Leishmania

“…Proteomics partially overcomes this hurdle: it has been extensively employed to decipher mechanisms of drug resistance [47][48][49], but this still overlooks some metabolic subtleties that are inherent to the complexity of the intracellular environment. A metabolome database for Leishmania has been developed [50], and a number comprehensive reviews have been published [51][52][53].…”

The Efficacy of L. (L.) chagasi Excreted-Secreted Antigens (ESAs) for Visceral Leishmaniasis Diagnosis Is Due To Low Levels of Cross-Reactivity

“…Although the molecules excreted and secreted by Leishmania spp. have been a target of interest for decades and have been identified as potential candidates for vaccines, 32 they have not been extensively explored for the diagnosis of leishmaniasis. 5,6,12,13,15 In this report, we present new data suggesting that ESAs isolated from three different species of Leishmania (from the most prevalent species in the Americas) L.…”

Comparative Analysis of the Omics Technologies Used to Study Antimonial, Amphotericin B, and Pentamidine Resistance inLeishmania

“…Essentially, it has been observed that most of the regulation in Leishmania is obtained posttranslationally. Hence proteomic studies provide more knowledge about differences between resistant and sensitive parasites as compared to genomic data [58]. It is a good indicator about protein abundance and expression and can yield an insight into species differences, stage differentiation, drug resistance, and virulence [59].…”

“…However, on the downside, a number of differentially expressed proteins found after proteome comparison lack an annotated function [57]. Most of the gel-based proteome comparisons only highlight abundant proteins, whereas the not-so-abundant ones seem to be masked [58]. Hence further research needs to be done in characterizing unidentified proteins, not-so-abundant proteins, and proteins with unknown functions.…”