The translatome of quiescent Plasmodium falciparum gametocytes reveals parasite pyridoxal 5’-phosphate (PLP) biosynthesis is essential for efficient mosquito stage development

@article{alves2026translatome,
  title = {{The translatome of quiescent Plasmodium falciparum gametocytes reveals parasite pyridoxal 5’-phosphate (PLP) biosynthesis is essential for efficient mosquito stage development}},
  author = {Eduardo Alves and Jack W. Houghton and Lindsay B. Stewart and Mufuliat T. Famodimu and Rosie Bridgwater and Mariana Reis Wunderlich and Naoki Matoba and Annie Z. Tremp and Michaela Bikarova and Jianan Lu and Mojca Kristan and Colin J. Sutherland and Edward W. Tate and Michael J. Delves},
  journal = {PLOS Pathogens},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.ppat.1014635},
  url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014635},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - The translatome of quiescent Plasmodium falciparum gametocytes reveals parasite pyridoxal 5’-phosphate (PLP) biosynthesis is essential for efficient mosquito stage development
AU  - Eduardo Alves
AU  - Jack W. Houghton
AU  - Lindsay B. Stewart
AU  - Mufuliat T. Famodimu
AU  - Rosie Bridgwater
AU  - Mariana Reis Wunderlich
AU  - Naoki Matoba
AU  - Annie Z. Tremp
AU  - Michaela Bikarova
AU  - Jianan Lu
AU  - Mojca Kristan
AU  - Colin J. Sutherland
AU  - Edward W. Tate
AU  - Michael J. Delves
PY  - 2026
DA  - 2026/09/23
JO  - PLOS Pathogens
DO  - 10.1371/journal.ppat.1014635
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014635
AB  - The ability of Plasmodium falciparum gametocytes to remain quiescent within the vertebrate host but poised for rapid onward development in the mosquito is an adaptation essential to maximise the onward spread of malaria. In this dormant state, mature infectious stage V gametocytes are largely unaffected by most antimalarial drugs and our limited understanding of how gametocytes prepare for mosquito transmission has hindered the identification of new molecular targets for transmission-blocking therapeutics. In this study, we move beyond the total proteome of gametocytes and define the translatome of mature stage V gametocytes using L-azidohomoalanine incorporation into nascent proteins, click chemistry purification and proteomic analysis. We identify the proteins and pathways that gametocytes sustain in preparation for transmission during this dormant period and through genetic disruption, we validate this approach by demonstrating the importance of parasite pyridoxal 5’-phosphate biosynthesis for mosquito transmission. Author summary: Malaria parasites rely on specialised sexual stages, called gametocytes, to transmit from humans to mosquitoes and continue their life cycle. Mature gametocytes can survive for long periods in the bloodstream in a dormant state, allowing them to persist after treatment and maintain transmission. However, little is known about how these cells prepare in advance life in the mosquito. Here, we examined which proteins mature Plasmodium falciparum gametocytes continue to make while they are waiting for transmission. Rather than measuring all proteins present in the cell, we identified those that were being actively produced over a 24-hour period. We found that mature gametocytes selectively invest in maintaining specific proteins and metabolic pathways that are likely important for survival and future development in the mosquito. Among the pathways prioritised was the production of pyridoxal 5′-phosphate, the active form of vitamin B6. By genetically disrupting this pathway, we showed that parasites could still produce viable gametocytes but were much less successful at developing inside mosquitoes. Our findings reveal biological processes that help malaria parasites prepare for transmission and highlight new opportunities for developing drugs that block the spread of malaria.
SN  - 1553-7374
ER  -