Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms

• Published in: PloS one Vol. 7; no. 10; p. e47913
• Main Authors: Lopez-Perez, Mary, Villasis, Elizabeth, Machado, Ricardo L D, Póvoa, Marinete M, Vinetz, Joseph M, Blair, Silvia, Gamboa, Dionicia, Lustigman, Sara
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Binding; Biology; Blood; Cloning; Enzymes; Erythrocytes; Erythrocytes - cytology; Erythrocytes - immunology; Erythrocytes - parasitology; Gene expression; Genetic aspects; Human populations; Humans; Humboldt, Alexander von (1769-1859); Infectious diseases; Laboratories; Ligands; Malaria; Malaria Vaccines - immunology; Malaria, Falciparum - genetics; Malaria, Falciparum - immunology; Malaria, Falciparum - metabolism; Malaria, Falciparum - parasitology; Medicine; Parasites; Parasitology; Pathways; Phenotype; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Plasmodium falciparum - pathogenicity; Polymorphism, Genetic; Population studies; Principal components analysis; Protein binding; Protein families; Proteins; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Proteins - metabolism; Public health; Reticulocytes - metabolism; Reticulocytes - parasitology; South America; Uniqueness; Vaccines; South America; Brazil; New York; Colombia; California; United States > US; Peru
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0047913

Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC) invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins, which are polymorphic and not fully characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1) and five members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5) families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr). Moreover, the invasion pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN variant. The ebl and Pfrh expression levels in a field isolate displaying the NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the major players in this invasion pathway. Notably, our studies demonstrate the uniqueness of the Peruvian P. falciparum field isolates in terms of their invasion profiles and ligand polymorphisms, and present a unique opportunity for studying the ability of P. falciparum parasites to expand their invasion repertoire after being reintroduced to human populations. The present study is directly relevant to asexual blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to preclude a simple one size fits all type of vaccine.