Proteome analysis of Plasmodium falciparum extracellular secretory antigens at asexual blood stages reveals a cohort of proteins with possible roles in immune modulation and signaling.
The highly co-evolved relationship of parasites and their hosts appears to include modulation of host immune signals, although the molecular mechanisms involved in the host-parasite interplay remain poorly understood. Characterization of these key genes and their cognate proteins related to the host-parasite interplay should lead to a better understanding of this intriguing biological phenomenon. The malaria agent Plasmodium falciparum is predicted to export a cohort of several hundred proteins to remodel the host erythrocyte. However, proteins actively exported by the asexual intracellular parasite beyond the host red blood cell membrane (before merozoite egress) have been poorly investigated so far. Here we used two complementary methodologies, two-dimensional gel electrophoresis/MS and LC-MS/MS, to examine the extracellular secreted antigens at asexual blood stages of P. falciparum. We identified 27 novel antigens exported by P. falciparum in the culture medium of which some showed clustering with highly polymorphic genes on chromosomes, suggesting that they may encode putative antigenic determinants of the parasite. Immunolocalization of four novel secreted proteins confirmed their export beyond the infected red blood cell membrane. Of these, preliminary functional characterization of two novel (Sel1 repeat-containing) parasite proteins, PfSEL1 and PfSEL2 revealed that they down-regulate expression of cell surface Notch signaling molecules in host cells. Also a novel protein kinase (PfEK) and a novel protein phosphatase (PfEP) were found to, respectively, phosphorylate/dephosphorylate parasite-specific proteins in the extracellular culture supernatant. Our study thus sheds new light on malaria parasite extracellular secreted antigens of which some may be essential for parasite development and could constitute promising new drug targets.
Singh
Meha
M
Malaria Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Mukherjee
Paushali
P
Narayanasamy
Krishnamoorthy
K
Arora
Reena
R
Sen
Som Dutta
SD
Gupta
Shashank
S
Natarajan
Krishnamurthy
K
Malhotra
Pawan
P
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D002853:Chromatography, Liquid; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D004912:Erythrocytes / Q000469:parasitology / Q000648:ultrastructure; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017125:Genes, Protozoan; D006801:Humans; D008018:Life Cycle Stages / Q000235:genetics / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood / Q000469:parasitology; D013058:Mass Spectrometry; D010271:Parasites / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development* / Q000276:immunology* / Q000648:ultrastructure; D020543:Proteome / Q000032:analysis* / Q000276:immunology; D015800:Protozoan Proteins / Q000032:analysis* / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic
D000953:Antigens, Protozoan; D020543:Proteome; D015800:Protozoan Proteins; D011994:Recombinant Proteins