Transcript and protein expression analysis of proteases in the blood stages of Plasmodium falciparum

Exp Parasitol. 2017 Sep;180:33-44. doi: 10.1016/j.exppara.2017.03.006. Epub 2017 Mar 27.

Abstract

Proteases are crucial enzymes with varying roles in living organisms. In the malaria parasite Plasmodium falciparum, the role of proteases has been deciphered mainly in the asexual blood stages and shown to represent promising drug targets. However, little is known about their functions in the sexual blood stages, which are important for transmission of the disease from the human to the mosquito vector. Determination of their stage-specific expression during the malaria life-cycle is crucial for the effective design of multi-stage anti-malaria drugs aimed at eradicating the disease. In this study, we screened the P. falciparum genome database for putative proteases and determined the transcript and protein expression profiles of selected proteases in the plasmodial blood stages using semi-quantitative RT-PCR and indirect immunofluorescence assay. Database mining identified a total of 148 putative proteases, out of which 18 were demonstrated to be expressed in the blood stages on the transcript level; for 12 of these proteins synthesis was confirmed. While three of these proteases exhibit gametocyte-specific expression, two are restricted to the asexual blood stages and seven are found in both stages, making them interesting multi-stage drug targets.

Keywords: Drug target; Gametocyte; Plasmodium falciparum; Proteases; Schizont; Transmission.

MeSH terms

  • Animals
  • Blotting, Western
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Immune Sera / immunology
  • Malaria, Falciparum / parasitology*
  • Mice
  • Parasitemia / parasitology*
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / immunology
  • Peptide Hydrolases / metabolism*
  • Plasmodium falciparum / enzymology*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism

Substances

  • Immune Sera
  • Recombinant Proteins
  • Peptide Hydrolases