Invasion profiles of Brazilian field isolates of Plasmodium falciparum: phenotypic and genotypic analyses.
The invasion of red blood cells (RBCs) by Plasmodium falciparum is dependent on multiple molecular interactions between erythrocyte receptors and parasite ligands. Invasion studies using culture-adapted parasite strains have indicated significant receptor heterogeneity. It is not known whether this heterogeneity reflects the parasite invasion arsenal in the field. We have studied the invasion phenotypes of 14 distinct field isolates from the Legal Amazon areas of Brazil by using erythrocyte invasion assays to investigate invasion into normal, enzyme-treated, and clinical-mutant RBCs. Analysis of these isolates revealed four distinct invasion profiles. Using En(a-) cells to get an unequivocal estimate of the use of glycophorin A (GPA) as a receptor, we found that the 175-kDa erythrocyte-binding antigen (EBA-175)/GPA pathway was used by a minority of the parasite isolates studied. Although polymorphism of region II domains at specific amino acid positions in both EBA-140 and EBA-181 was found in these field isolates, this did not correlate with invasion profiles and thus receptor selectivity. These studies have further confirmed the existence of a significant diversity of invasion pathways in nature and suggest that additional parasite ligands will have to be targeted to devise global vaccines that will work in the field.
Lobo
Cheryl-Ann
CA
Molecular Parasitology, Lindsley Kimball Research Institute, New York Blood Center, New York, New York 10021, USA. clobo@nybloodcenter.org
de Frazao
Karla
K
Rodriguez
Marilis
M
Reid
Marion
M
Zalis
Mariano
M
Lustigman
Sara
S
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics; D001938:Brazil; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002999:Clone Cells / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010641:Phenotype; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*
D000953:Antigens, Protozoan; D002352:Carrier Proteins; C474029:EBA-181 protein, Plasmodium falciparum; C438380:EBA140 protein, Plasmodium falciparum; D008565:Membrane Proteins; D015800:Protozoan Proteins