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<p>The <i>Plasmodium</i> infection cycle in mosquitoes relies on numerous host factors in the vector midgut, which can be targeted with therapeutics. The mosquito prefoldin complex is needed to fold proteins and macromolecular complexes properly. Here we show that the conserved <i>Anopheles</i> mosquito prefoldin (PFDN)–chaperonin system is a potent transmission-blocking target for multiple <i>Plasmodium</i> species. Silencing any prefoldin subunit or its CCT/TRiC partner via RNA interference reduces <i>Plasmodium falciparum</i> oocyst loads in the mosquito midgut, as does co-feeding mosquitoes with PFDN6-specific antibody and gametocytes. Inhibition of the PFDN–CCT/TRiC chaperonin complex results in the loss of epithelial and extracellular matrix integrity, which triggers microorganism-mediated anti-<i>Plasmodium</i> immune priming and compromises the parasite’s laminin-based immune evasion. Mouse malaria transmission-blocking vaccine and antibody co-feeding assays support its potential as a multispecies transmission-blocking target for <i>P. falciparum</i> and <i>Plasmodium vivax</i>. Further study is needed to determine the potential of this system as a transmission-blocking vaccine target.</p>

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Targeting the mosquito prefoldin–chaperonin complex blocks Plasmodium transmission

  • 期刊论文

  • 发表日期：

    2025年3月6日

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  • Yuemei Dong,
  • Seokyoung Kang,
  • Simone L. Sandiford,
  • Andrew Pike,
  • Maria L. Simões,
  • Ratawan Ubalee,
  • Kevin Kobylinski,
  • George Dimopoulos

摘要

The Plasmodium infection cycle in mosquitoes relies on numerous host factors in the vector midgut, which can be targeted with therapeutics. The mosquito prefoldin complex is needed to fold proteins and macromolecular complexes properly. Here we show that the conserved Anopheles mosquito prefoldin (PFDN)–chaperonin system is a potent transmission-blocking target for multiple Plasmodium species. Silencing any prefoldin subunit or its CCT/TRiC partner via RNA interference reduces Plasmodium falciparum oocyst loads in the mosquito midgut, as does co-feeding mosquitoes with PFDN6-specific antibody and gametocytes. Inhibition of the PFDN–CCT/TRiC chaperonin complex results in the loss of epithelial and extracellular matrix integrity, which triggers microorganism-mediated anti-Plasmodium immune priming and compromises the parasite’s laminin-based immune evasion. Mouse malaria transmission-blocking vaccine and antibody co-feeding assays support its potential as a multispecies transmission-blocking target for P. falciparum and Plasmodium vivax. Further study is needed to determine the potential of this system as a transmission-blocking vaccine target.