title: A novel Plasmodium falciparum rhoptry associated adhesin mediates erythrocyte invasion through the sialic-acid dependent pathway.
abstract: Erythrocyte invasion by Plasmodium falciparum merozoites is central to blood-stage infection and malaria pathogenesis. This intricate process is coordinated by multiple parasite adhesins that bind erythrocyte receptors and mediate invasion through several alternate pathways. P. falciparum expresses 2700 genes during the blood-stages, of which the identity and function of many remains unknown. Here, we have identified and characterized a novel P. falciparum rhoptry associated adhesin (PfRA) that mediates erythrocyte invasion through the sialic-acid dependent pathway. PfRA appears to play a significant functional role as it is conserved across different Plasmodium species. It is localized in the rhoptries and further translocated to the merozoite surface. Both native and recombinant PfRA specifically bound erythrocytes in a sialic-acid dependent, chymotrypsin and trypsin resistant manner, which was abrogated by PfRA antibodies confirming a role in erythrocyte invasion. PfRA antibodies inhibited erythrocyte invasion and in combination with antibodies against other parasite ligands produced an additive inhibitory effect, thus validating its important role in erythrocyte invasion. We have thus identified a novel P. falciparum adhesin that binds with a sialic acid containing erythrocyte receptor. Our observations substantiate the strategy to block P. falciparum erythrocyte invasion by simultaneously targeting multiple conserved merozoite antigens involved in alternate invasion pathways.
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Anand
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: K Sony
authors.initials: KS
authors.lastname: Reddy
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Syed Yusuf
authors.initials: SY
authors.lastname: Mian
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Hina
authors.initials: H
authors.lastname: Singh
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Shivani Arora
authors.initials: SA
authors.lastname: Mittal
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Amlabu
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saude de Manhiça (CISM), Maputo, Mozambique.
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.affiliation: ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.|Centro de Investigação em Saude de Manhiça (CISM), Maputo, Mozambique.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
authors.forename: Virander Singh
authors.initials: VS
authors.lastname: Chauhan
authors.affiliation: Laboratory of Malaria and Vaccine Research, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Gaur
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D008018:Life Cycle Stages; D052940:Merozoites / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010271:Parasites / Q000254:growth & development; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D011485:Protein Binding; D021381:Protein Transport; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility
chemical_list: D015800:Protozoan Proteins; D011994:Recombinant Proteins; C065352:rhoptry associated protein, Plasmodium; D019158:N-Acetylneuraminic Acid