title: Whole-transcriptome analysis of Plasmodium falciparum field isolates: identification of new pathogenicity factors.
abstract: BACKGROUND
  Severe malaria and one of its most important pathogenic processes, cerebral malaria, involves the sequestration of parasitized red blood cells (pRBCs) in brain postcapillary venules. Although the pathogenic mechanisms underlying malaria remain poorly characterized, it has been established that adhesion of pRBCs to endothelial cells (ECs) can result in cell apoptosis, which in turn may lead to disruption of the blood-brain barrier. The nature of the parasite molecules involved in the pathogenesis of severe malaria remains elusive.
  
  
  METHODS
  Whole-transcriptome profiling of nonapoptogenic versus apoptogenic parasite field isolates obtained from Gabonese children was performed with pan-genomic Plasmodium falciparum DNA microarrays; radiolabeled instead of fluorescent cDNAs were used to improve the sensitivity of signal detection.
  
  
  RESULTS
  Our methods allowed the identification of 59 genes putatively associated with the induction of EC apoptosis. Silencing of Plasmodium gene expression with specific double-stranded RNA was performed on 8 selected genes; 5 of these, named "Plasmodium apoptosis-linked pathogenicity factors" (PALPFs), were found to be linked to parasite apoptogenicity. Of these genes, 2 might act via parasite cytoadherence.
  
  
  CONCLUSIONS
  This is the first attempt to identify genes involved in parasite pathogenic mechanisms against human ECs. The finding of PALPFs illuminates perspectives for novel therapeutic strategies against cerebral complications of malaria.
authors.affiliation: Institut National de la Sante et de la Recherche Medicale U511, Paris 75013, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Siau
authors.forename: Fousseyni S
authors.initials: FS
authors.lastname: Toure
authors.forename: Odile
authors.initials: O
authors.lastname: Ouwe-Missi-Oukem-Boyer
authors.forename: Liliane
authors.initials: L
authors.lastname: Ciceron
authors.forename: Nassira
authors.initials: N
authors.lastname: Mahmoudi
authors.forename: Catherine
authors.initials: C
authors.lastname: Vaquero
authors.forename: Patrick
authors.initials: P
authors.lastname: Froissard
authors.forename: Ulrick
authors.initials: U
authors.lastname: Bisvigou
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bisser
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppee
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
mesh_terms: D000818:Animals; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000469:parasitology; D001921:Brain / Q000469:parasitology*; D002448:Cell Adhesion; D002648:Child; D016054:DNA, Protozoan / Q000032:analysis*; D042783:Endothelial Cells / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology; D005681:Gabon; D020869:Gene Expression Profiling; D017125:Genes, Protozoan; D006801:Humans; D016779:Malaria, Cerebral / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000175:diagnosis*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037521:Virulence Factors
chemical_list: D016054:DNA, Protozoan; D037521:Virulence Factors