Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding protein

Handle URI:
http://hdl.handle.net/10754/325342
Title:
Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding protein
Authors:
Ogun, Solabomi A.; Tewari, Rita; Otto, Thomas D.; Howell, Steven A.; Knuepfer, Ellen; Cunningham, Deirdre A.; Xu, Zhengyao; Pain, Arnab ( 0000-0002-1755-2819 ) ; Holder, Anthony A.
Abstract:
Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional redundancy at the protein level gives the parasite phenotypic plasticity in the absence of differences in gene expression. © 2011 Ogun et al.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division; Computational Bioscience Research Center (CBRC)
Citation:
Ogun SA, Tewari R, Otto TD, Howell SA, Knuepfer E, et al. (2011) Targeted Disruption of py235ebp-1: Invasion of Erythrocytes by Plasmodium yoelii Using an Alternative Py235 Erythrocyte Binding Protein. PLoS Pathog 7: e1001288. doi:10.1371/journal.ppat.1001288.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS Pathogens
Issue Date:
17-Feb-2011
DOI:
10.1371/journal.ppat.1001288
PubMed ID:
21379566
PubMed Central ID:
PMC3040676
Type:
Article
ISSN:
15537366
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorOgun, Solabomi A.en
dc.contributor.authorTewari, Ritaen
dc.contributor.authorOtto, Thomas D.en
dc.contributor.authorHowell, Steven A.en
dc.contributor.authorKnuepfer, Ellenen
dc.contributor.authorCunningham, Deirdre A.en
dc.contributor.authorXu, Zhengyaoen
dc.contributor.authorPain, Arnaben
dc.contributor.authorHolder, Anthony A.en
dc.date.accessioned2014-08-27T09:48:06Z-
dc.date.available2014-08-27T09:48:06Z-
dc.date.issued2011-02-17en
dc.identifier.citationOgun SA, Tewari R, Otto TD, Howell SA, Knuepfer E, et al. (2011) Targeted Disruption of py235ebp-1: Invasion of Erythrocytes by Plasmodium yoelii Using an Alternative Py235 Erythrocyte Binding Protein. PLoS Pathog 7: e1001288. doi:10.1371/journal.ppat.1001288.en
dc.identifier.issn15537366en
dc.identifier.pmid21379566en
dc.identifier.doi10.1371/journal.ppat.1001288en
dc.identifier.urihttp://hdl.handle.net/10754/325342en
dc.description.abstractPlasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional redundancy at the protein level gives the parasite phenotypic plasticity in the absence of differences in gene expression. © 2011 Ogun et al.en
dc.language.isoenen
dc.publisherPublic Library of Science (PLoS)en
dc.rightsOgun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.rightsArchived with thanks to PLoS Pathogensen
dc.subjectmicroorganism proteinen
dc.subjectmonoclonal antibodyen
dc.subjectpy235 erythrocyte binding proteinen
dc.subjectunclassified drugen
dc.subjectdiagnostic agenten
dc.subjectmessenger RNAen
dc.subjectparasite antigenen
dc.subjectcontrolled studyen
dc.subjecterythrocyteen
dc.subjectgene deletionen
dc.subjectgene dosageen
dc.subjecthost pathogen interactionen
dc.subjectmerozoiteen
dc.subjectmicrobial growthen
dc.subjectPlasmodium yoeliien
dc.subjectprotein analysisen
dc.subjectprotein expressionen
dc.subjectprotein functionen
dc.subjectreverse transcription polymerase chain reactionen
dc.subjectwild typeen
dc.subjectalternative RNA splicingen
dc.subjectamino acid sequenceen
dc.subjectBagg albino mouseen
dc.subjecterythrocyteen
dc.subjecterythrocyte counten
dc.subjectfluorescent antibody techniqueen
dc.subjectgene deletionen
dc.subjectgeneticsen
dc.subjectgenomeen
dc.subjectgrowth, development and agingen
dc.subjectimmunologyen
dc.subjectimmunoprecipitationen
dc.subjectmalariaen
dc.subjectmass spectrometryen
dc.subjectmetabolismen
dc.subjectmolecular geneticsen
dc.subjectmouseen
dc.subjectmouse mutanten
dc.subjectmultigene familyen
dc.subjectparasitologyen
dc.subjectpathogenicityen
dc.subjectsequence homologyen
dc.subjectSouthern blottingen
dc.subjectWestern blottingen
dc.subjectPlasmodium falciparumen
dc.subjectPlasmodium vivaxen
dc.subjectPlasmodium yoeliien
dc.subjectAlternative Splicingen
dc.subjectAmino Acid Sequenceen
dc.subjectAntibodies, Monoclonalen
dc.subjectAntigens, Protozoanen
dc.subjectBlotting, Southernen
dc.subjectBlotting, Westernen
dc.subjectErythrocyte Counten
dc.subjectErythrocytesen
dc.subjectFluorescent Antibody Techniqueen
dc.subjectGene Deletionen
dc.subjectGenome, Protozoanen
dc.subjectImmunoprecipitationen
dc.subjectMalariaen
dc.subjectMiceen
dc.subjectMice, Inbred BALB Cen
dc.subjectMice, Knockouten
dc.subjectMolecular Sequence Dataen
dc.subjectMultigene Familyen
dc.subjectPlasmodium yoeliien
dc.subjectReverse Transcriptase Polymerase Chain Reactionen
dc.subjectRNA, Messengeren
dc.subjectSequence Homology, Amino Aciden
dc.subjectSpectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationen
dc.titleTargeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding proteinen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalPLoS Pathogensen
dc.identifier.pmcidPMC3040676en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionDivision of Parasitology, MRC National Institute for Medical Research, London, United Kingdomen
dc.contributor.institutionInstitute of Genetics, University of Nottingham, Nottingham, United Kingdomen
dc.contributor.institutionParasite Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdomen
dc.contributor.institutionProtein Structure, MRC National Institute for Medical Research, London, United Kingdomen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorPain, Arnaben
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