Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage

Elena Deligianni, Natalie C. Silmon de Monerri, Paul J. McMillan, Lucia Bertuccini, Fabiana Superti, Maria Manola, Lefteris Spanos, Christos Louis, Michael J. Blackman, Leann Tilley, Inga Siden-Kiamos

Research output: Contribution to journalArticle

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Abstract

Pore forming proteins such as those belonging to the membrane attack/perforin (MACPF) family have important functions in many organisms. Of the five MACPF proteins found in Plasmodium parasites, three have functions in cell passage and one in host cell egress. Here we report an analysis of the perforin-like protein 4, PPLP4, in the rodent parasite Plasmodium berghei. We found that the protein is expressed only in the ookinete, the invasive stage of the parasite formed in the mosquito midgut. Transcriptional analysis revealed that expression of the pplp4 gene commences during ookinete development. The protein was detected in retorts and mature ookinetes. Using two antibodies, the protein was found localized in a dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein however showed mainly cytoplasmic label. A pplp4 null mutant formed motile ookinetes, but these were unable to invade and traverse the midgut epithelium resulting in severely impaired oocyst formation and no transmission to naïve mice. However, when in vitro cultured ookinetes were injected into the thorax of the mosquito, thus by-passing midgut passage, sporozoites were formed and the mutant parasites were able to infect naïve mice. Taken together, our data show that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the question why three proteins with MACPF domains are needed for invasion by the ookinete of the mosquito midgut epithelium.

Original languageEnglish
Article numbere0201651
JournalPLoS One
Volume13
Issue number8
DOIs
Publication statusPublished - Aug 1 2018

Fingerprint

ookinetes
Perforin
Plasmodium
midgut
Culicidae
Parasites
Proteins
proteins
parasites
Membranes
Epithelium
Plasmodium berghei
Sporozoites
Porins
epithelium
Oocysts
mutants
sporozoites
mice
Rodentia

Keywords

  • Plasmodium

ASJC Scopus subject areas

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

Cite this

Deligianni, E., Silmon de Monerri, N. C., McMillan, P. J., Bertuccini, L., Superti, F., Manola, M., ... Siden-Kiamos, I. (2018). Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage. PLoS One, 13(8), [e0201651]. https://doi.org/10.1371/journal.pone.0201651

Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage. / Deligianni, Elena; Silmon de Monerri, Natalie C.; McMillan, Paul J.; Bertuccini, Lucia; Superti, Fabiana; Manola, Maria; Spanos, Lefteris; Louis, Christos; Blackman, Michael J.; Tilley, Leann; Siden-Kiamos, Inga.

In: PLoS One, Vol. 13, No. 8, e0201651, 01.08.2018.

Research output: Contribution to journalArticle

Deligianni, E, Silmon de Monerri, NC, McMillan, PJ, Bertuccini, L, Superti, F, Manola, M, Spanos, L, Louis, C, Blackman, MJ, Tilley, L & Siden-Kiamos, I 2018, 'Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage', PLoS One, vol. 13, no. 8, e0201651. https://doi.org/10.1371/journal.pone.0201651
Deligianni, Elena ; Silmon de Monerri, Natalie C. ; McMillan, Paul J. ; Bertuccini, Lucia ; Superti, Fabiana ; Manola, Maria ; Spanos, Lefteris ; Louis, Christos ; Blackman, Michael J. ; Tilley, Leann ; Siden-Kiamos, Inga. / Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage. In: PLoS One. 2018 ; Vol. 13, No. 8.
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