title: A Novel and Conserved Plasmodium Sporozoite Membrane Protein SPELD is Required for Maturation of Exo-erythrocytic Forms.
abstract: Plasmodium sporozoites are the infective forms of malaria parasite to vertebrate host and undergo dramatic changes in their transcriptional repertoire during maturation in mosquito salivary glands. We report here the role of a novel and conserved Plasmodium berghei protein encoded by PBANKA_091090 in maturation of Exo-erythrocytic Forms (EEFs) and designate it as Sporozoite surface Protein Essential for Liver stage Development (PbSPELD). PBANKA_091090 was previously annotated as PB402615.00.0 and its transcript was recovered at maximal frequency in the Serial Analysis of the Gene Expression (SAGE) of Plasmodium berghei salivary gland sporozoites. An orthologue of this transcript was independently identified in Plasmodium vivax sporozoite microarrays and was designated as Sporozoite Conserved Orthologous Transcript-2 (scot-2). Functional characterization through reverse genetics revealed that PbSPELD is essential for Plasmodium liver stage maturation. mCherry transgenic of PbSPELD localized the protein to plasma membrane of sporozoites and early EEFs. Global microarray analysis of pbspeld ko revealed EEF attenuation being associated with down regulation of genes central to general transcription, cell cycle, proteosome and cadherin signaling. pbspeld mutant EEFs induced pre-erythrocytic immunity with 50% protective efficacy. Our studies have implications for attenuating the human Plasmodium liver stages by targeting SPELD locus.
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Faisal Mohammed Abdul
authors.initials: FM
authors.lastname: Al-Nihmi
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Kolli
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Segireddy Rameswara
authors.initials: SR
authors.lastname: Reddy
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Babu S
authors.initials: BS
authors.lastname: Mastan
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Togiri
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Mulaka
authors.initials: M
authors.lastname: Maruthi
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Roshni
authors.initials: R
authors.lastname: Gupta
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Habsiguda, Uppal Road, Hyderabad 500007, India.
authors.forename: Puran Singh
authors.initials: PS
authors.lastname: Sijwali
authors.affiliation: Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India.
authors.forename: Satish
authors.initials: S
authors.lastname: Mishra
authors.affiliation: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
authors.forename: Kota Arun
authors.initials: KA
authors.lastname: Kumar
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D017124:Conserved Sequence; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005260:Female; D018628:Gene Dosage; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D056945:Hep G2 Cells; D006801:Humans; D007109:Immunity; D007114:Immunization; D008018:Life Cycle Stages; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000635:transmission; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010962:Plasmodium berghei / Q000254:growth & development* / Q000378:metabolism*; D000072417:Protein Domains; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism; D013045:Species Specificity; D034101:Sporozoites / Q000254:growth & development / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins