Genome-wide identification of molecular mimicry candidates in parasites

PloS One
Philipp LudinPascal Mäser

Abstract

Among the many strategies employed by parasites for immune evasion and host manipulation, one of the most fascinating is molecular mimicry. With genome sequences available for host and parasite, mimicry of linear amino acid epitopes can be investigated by comparative genomics. Here we developed an in silico pipeline for genome-wide identification of molecular mimicry candidate proteins or epitopes. The predicted proteome of a given parasite was broken down into overlapping fragments, each of which was screened for close hits in the human proteome. Control searches were carried out against unrelated, free-living eukaryotes to eliminate the generally conserved proteins, and with randomized versions of the parasite proteins to get an estimate of statistical significance. This simple but computation-intensive approach yielded interesting candidates from human-pathogenic parasites. From Plasmodium falciparum, it returned a 14 amino acid motif in several of the PfEMP1 variants identical to part of the heparin-binding domain in the immunosuppressive serum protein vitronectin. And in Brugia malayi, fragments were detected that matched to periphilin-1, a protein of cell-cell junctions involved in barrier formation. All the results are p...Continue Reading

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Apr 29, 2014·The Journal of Parasitology·Eric J McElroy, I de Buron
Feb 14, 2016·International Journal for Parasitology·Pengfei CaiDonald P McManus
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Software Mentioned

ClustalX
ClustalW
mimicDB
EMBOSS package
MySQL
Phobius
Perl scripts
Perl
BLAST
CRIT

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