Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium

Zoi Tampaki, Ramadhan S. Mwakubambanya, Evi Goulielmaki, Sofia Kaforou, Kami Kim, Andrew P. Waters, Vern B. Carruthers, Inga Siden-Kiamos, Thanasis G. Loukeris, Konstantinos Koussis

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Regulated proteolysis is known to control a variety of vital processes in apicomplexan parasites including invasion and egress of host cells. Serine proteases have been proposed as targets for drug development based upon inhibitor studies that show parasite attenuation and transmission blockage. Genetic studies suggest that serine proteases, such as subtilisin and rhomboid proteases, are essential but functional studies have proved challenging as active proteases are difficult to express. Proteinaceous Protease Inhibitors (PPIs) provide an alternative way to address the role of serine proteases in apicomplexan biology. To validate such an approach, a Neospora caninum Kazal inhibitor (NcPI-S) was expressed ectopically in two apicomplexan species, Toxoplasma gondii tachyzoites and Plasmodium berghei ookinetes, with the aim to disrupt proteolytic processes taking place within the secretory pathway. NcPI-S negatively affected proliferation of Toxoplasma tachyzoites, while it had no effect on invasion and egress. Expression of the inhibitor in P. berghei zygotes blocked their development into mature and invasive ookinetes. Moreover, ultra-structural studies indicated that expression of NcPI-S interfered with normal formation of micronemes, which was also confirmed by the lack of expression of the micronemal protein SOAP in these parasites. Our results suggest that NcPI-S could be a useful tool to investigate the function of proteases in processes fundamental for parasite survival, contributing to the effort to identify targets for parasite attenuation and transmission blockage.

Original languageEnglish (US)
Article numbere0121379
JournalPLoS One
Volume10
Issue number3
DOIs
StatePublished - Mar 24 2015

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Neospora
Toxoplasma
Plasmodium
Neospora caninum
Parasites
parasites
Serine Proteases
serine proteinases
Defects
ookinetes
Plasmodium berghei
tachyzoites
Peptide Hydrolases
proteinases
Proteolysis
Subtilisin
subtilisin
Zygote
Secretory Pathway
zygote

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Tampaki, Z., Mwakubambanya, R. S., Goulielmaki, E., Kaforou, S., Kim, K., Waters, A. P., ... Koussis, K. (2015). Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium. PLoS One, 10(3), [e0121379]. https://doi.org/10.1371/journal.pone.0121379

Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium. / Tampaki, Zoi; Mwakubambanya, Ramadhan S.; Goulielmaki, Evi; Kaforou, Sofia; Kim, Kami; Waters, Andrew P.; Carruthers, Vern B.; Siden-Kiamos, Inga; Loukeris, Thanasis G.; Koussis, Konstantinos.

In: PLoS One, Vol. 10, No. 3, e0121379, 24.03.2015.

Research output: Contribution to journalArticle

Tampaki, Z, Mwakubambanya, RS, Goulielmaki, E, Kaforou, S, Kim, K, Waters, AP, Carruthers, VB, Siden-Kiamos, I, Loukeris, TG & Koussis, K 2015, 'Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium', PLoS One, vol. 10, no. 3, e0121379. https://doi.org/10.1371/journal.pone.0121379
Tampaki, Zoi ; Mwakubambanya, Ramadhan S. ; Goulielmaki, Evi ; Kaforou, Sofia ; Kim, Kami ; Waters, Andrew P. ; Carruthers, Vern B. ; Siden-Kiamos, Inga ; Loukeris, Thanasis G. ; Koussis, Konstantinos. / Ectopic expression of a Neospora caninum Kazal type inhibitor triggers developmental defects in Toxoplasma and Plasmodium. In: PLoS One. 2015 ; Vol. 10, No. 3.
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