Quantitative Proteome Analysis of Leishmania donovani under Spermidine Starvation

PLoS One. 2016 Apr 28;11(4):e0154262. doi: 10.1371/journal.pone.0154262. eCollection 2016.

Abstract

We have earlier reported antileishmanial activity of hypericin by spermidine starvation. In the current report, we have used label free proteome quantitation approach to identify differentially modulated proteins after hypericin treatment. A total of 141 proteins were found to be differentially regulated with ANOVA P value less than 0.05 in hypericin treated Leishmania promastigotes. Differentially modulated proteins have been broadly classified under nine major categories. Increase in ribosomal protein S7 protein suggests the repression of translation. Inhibition of proteins related to ubiquitin proteasome system, RNA binding protein and translation initiation factor also suggests altered translation. We have also observed increased expression of Hsp 90, Hsp 83-1 and stress inducible protein 1. Significant decreased level of cyclophilin was observed. These stress related protein could be cellular response of the parasite towards hypericin induced cellular stress. Also, defective metabolism, biosynthesis and replication of nucleic acids, flagellar movement and signalling of the parasite were observed as indicated by altered expression of proteins involved in these pathways. The data was analyzed rigorously to get further insight into hypericin induced parasitic death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes
  • Antiprotozoal Agents / pharmacology*
  • Cyclophilins / genetics
  • Cyclophilins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Leishmania donovani / drug effects*
  • Leishmania donovani / genetics
  • Leishmania donovani / growth & development
  • Leishmania donovani / metabolism
  • Life Cycle Stages / drug effects*
  • Life Cycle Stages / genetics
  • Molecular Sequence Annotation
  • Peptide Chain Initiation, Translational / drug effects
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology
  • Proteome / genetics*
  • Proteome / metabolism
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Spermidine / metabolism*
  • Ubiquitin / genetics
  • Ubiquitin / metabolism

Substances

  • Anthracenes
  • Antiprotozoal Agents
  • Heat-Shock Proteins
  • Proteome
  • Protozoan Proteins
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • Ubiquitin
  • ribosomal protein S7
  • Perylene
  • hypericin
  • Cyclophilins
  • Spermidine

Grants and funding

Research fellowships to SS by IIT Guwahati are acknowledged. Financial support by Department of Biotechnology, Government of India in the form of research grant (Project no: BT/555/NE/U-Excel/2014) to VKD is also acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.