Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein

Kazura, J. W., Ogun, S. A., Tewari, R., Otto, T. D. , Howell, S. A., Knuepfer, E., Cunningham, D. A., Xu, Z., Pain, A. and Holder, A. A. (2011) Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein. PLoS Pathogens, 7(2), e1001288. (doi: 10.1371/journal.ppat.1001288) (PMID:21379566) (PMCID:PMC3040676)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas
• Authors: Kazura, J. W., Ogun, S. A., Tewari, R., Otto, T. D., Howell, S. A., Knuepfer, E., Cunningham, D. A., Xu, Z., Pain, A., and Holder, A. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Copyright Holders: Copyright ©2011 The Authors
• First Published: First published in PLoS Genetics 7(2):e10012889
• Publisher Policy: Reproduced under a Creative Commons License