title: The repeat region of the circumsporozoite protein is critical for sporozoite formation and maturation in Plasmodium.
abstract: The circumsporozoite protein (CSP) is the major surface protein of the sporozoite stage of malaria parasites and has multiple functions as the parasite develops and then migrates from the mosquito midgut to the mammalian liver. The overall structure of CSP is conserved among Plasmodium species, consisting of a species-specific central tandem repeat region flanked by two conserved domains: the NH2-terminus and the thrombospondin repeat (TSR) at the COOH-terminus. Although the central repeat region is an immunodominant B-cell epitope and the basis of the only candidate malaria vaccine in Phase III clinical trials, little is known about its functional role(s). We used the rodent malaria model Plasmodium berghei to investigate the role of the CSP tandem repeat region during sporozoite development. Here we describe two mutant parasite lines, one lacking the tandem repeat region (ΔRep) and the other lacking the NH2-terminus as well as the repeat region (ΔNΔRep). We show that in both mutant lines oocyst formation is unaffected but sporozoite development is defective.
authors.affiliation: Nuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom.
authors.forename: David J P
authors.initials: DJ
authors.lastname: Ferguson
authors.affiliation: Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Balaban
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG2 7UH, United Kingdom.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Patzewitz
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG2 7UH, United Kingdom.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wall
authors.affiliation: Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Hopp
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG2 7UH, United Kingdom.
authors.forename: Benoit
authors.initials: B
authors.lastname: Poulin
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi-110067, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Mohmmed
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi-110067, India.
authors.forename: Pawan
authors.initials: P
authors.lastname: Malhotra
authors.affiliation: Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Alida
authors.initials: A
authors.lastname: Coppi
authors.affiliation: Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Photini
authors.initials: P
authors.lastname: Sinnis
authors.affiliation: Centre for Genetics and Genomics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, NG2 7UH, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Tewari
mesh_terms: D000818:Animals; D008288:Malaria / Q000469:parasitology*; D010962:Plasmodium berghei / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D034101:Sporozoites / Q000737:chemistry / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan