Targeted Disruption of : Invasion of
Erythrocytes by Using an Alternative Py235
Erythrocyte Binding Protein
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.
Vyšlo v časopise:
Targeted Disruption of : Invasion of
Erythrocytes by Using an Alternative Py235
Erythrocyte Binding Protein. PLoS Pathog 7(2): e32767. doi:10.1371/journal.ppat.1001288
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001288
Souhrn
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.
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