Differentially modulated proteins associated with Leishmaniasis—a systematic review of in-vivo and in-vitro studies

Abstract

High-throughput proteomic technologies are widely used for understanding the disease mechanism, drug-resistant mechanism, and to identify drug targets and markers for diagnostics. Studies with proteomics applications, relating to Leishmaniasis, are being constantly reported in the literature. However, from such studies, a readily accessible knowledge of differentially modulated proteins associated with Leishmaniasis is lacking. Hence, we performed a systematic review concerning differentially modulated proteins (DMP) in Leishmania as well as host infected with Leishmania from the published articles between the years 2000 and 2019. This review is classified into five different sections, namely, DMP in the host after Leishmania infection, DMP between different strains of Leishmania , DMP in drug-resistant Leishmania , DMP in Leishmania under stress, and DMP in different life stages of Leishmania. A lot of consensuses could be observed among the DMP in drug-resistant and stressed Leishmania . In addition to the review, a database was constructed with the data collected in this study (protein accession ID, protein name, gene name, host organism, experimental conditions, fold change, and regulatory data). A total of 2635 records are available in the database. We believe this review and the database will help the researcher in understanding the disease better and provide information for the targeted proteomics study related to Leishmaniasis. Database availability: http://ldepdb.biomedinformri.com/ . Electronic supplementary material The online version of this article (10.1007/s11033-020-05936-z) contains supplementary material, which is available to authorized users.

In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase

“…However, these drug treatments suffer from one or more limitations, such as treatment failure (Ponte-Sucre et al 2017 ), resistance (Horacio et al 2021 ), longer half-life (Reimao et al 2020 ), relapses after treatment (Araújo et al 2021 ), toxicity (Arenas et al 2017 ), or higher cost (Azim et al 2021 ). Considering the absence of a vaccine, a number of alternative strategies are being researched from a range of significant pathways to create a new drug for the disease (Ranjan et al 2020 ; Vijayakumar et al 2019 ; Vijayakumar and Das 2018 ). Some common pathways being targeted include, but are not limited to, purine salvage pathway (Brindha et al 2021 ), ergosterol biosynthesis pathway (McCall et al 2015 ), polyamine biosynthesis pathway (Da Silva et al 2012 ), and thiol metabolism pathway (Singh et al 2017 ).…”

Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony

“…Finally, studies related to the ribosome have found differential expression of the proteins of the large subunit (e.g., L23a) involved in translation and with a role in kinase activity in Leishmania resistant to pentavalent antimonials, miltefosine, and amphotericin [ 97 , 98 ]. Likewise, ribosomal proteins play a role in cell growth and apoptosis control [ 99 ] (Fig. 5 c; Additional file 5 : Table S5).…”

Characterization of a novel amastin-like surface protein (ALSP) of Leishmania donovani, a probable lipase

“…The glycerol from hydrolysed lipid is transported across to the parasite from the host cell through aquaporin AQP1-like aquaglyceroporin channels, contributing to the complex energy metabolism of the parasite (Frezard et al, 2014). Glycerol-transport proteins have been predicted to be present in L. donovani (Ranjan et al, 2020). Fatty acids, derived from the host, are transported back to the parasite by complex mechanisms (Berman et al, 1987, Ramakrishnan et al, 2013).…”

“…The solitary expression of ALSP in amastigotes rather than promastigotes is an exceptional phenomenon, as only a percentage of proteins are differentially expressed between these morphological forms. For the most part, all proteins are constitutively expressed in both promastigotes and amastigotes, making it non-selective for the parasite to survive in the invertebrate and human host (Leifso et al, 2007; Ranjan et al, 2020). Additionally, bioinformatics prediction and the current study indicates differential expression of ALSP in different species of Leishmania ( donovani vs. major ), which also is an intriguing observation.…”

“…Glycerol-transport proteins have been predicted to be present in L. donovani (Ranjan et al, 2020). Fatty acids, derived from the host, are transported back to the parasite by complex mechanisms (Berman et al, 1987, Ramakrishnan et al, 2013.…”