Plasmodium thiamine pyrophosphokinase is essential for sporozoite formation and activation of an antiplasmodial thiamine analogue
Proceedings of the National Academy of Sciences·
- DOI
- 10.1073/pnas.2534594123
- PMID
- 42640797
- PMCID
- —
- OpenAlex
- —
- Study type
- Journal article
- Publisher
- National Academy of Sciences
- Article type
- journal-article
- Integrity
- current
Why this research matters now
TPK plays a critical role in sporogony within the mosquito vector, supporting its potential as a transmission-blocking target for antimalarial intervention.
Structured evidence summary
Research question
The study investigated the mechanism by which oxythiamine inhibits Plasmodium parasites and examined the role of thiamine pyrophosphokinase (TPK) across the parasite life cycle.
Study design
Researchers generated oxythiamine-resistant P. falciparum lines through in vitro drug pressure and performed whole-genome sequencing. A TPK-knockout line was created in P. berghei to assess fitness costs, drug sensitivity in vivo, and oocyst and sporozoite development in Anopheles mosquitoes.
Population and setting
The study used laboratory models of P. falciparum and P. berghei parasites, including intraerythrocytic stages and transmission through Anopheles mosquito vectors.
Main findings
A single-point mutation in the TPK gene conferred oxythiamine resistance by reducing TPK activity and limiting conversion of oxythiamine to its toxic form. TPK-knockout parasites showed minor intraerythrocytic fitness costs and fivefold reduced oxythiamine sensitivity in vivo. In mosquitoes, TPK-knockout parasites formed oocysts but exhibited impaired maturation and complete inhibition of sporozoite formation.
Public-health relevance
TPK plays a critical role in sporogony within the mosquito vector, supporting its potential as a transmission-blocking target for antimalarial intervention.
Important limitations
This summary relies on the supplied single-article abstract and metadata. Full interpretation of study validity, generalizability, and translational implications requires review of the complete published paper.
GIDS interpretation
The article was classified under Malaria and Transmission dynamics, reflecting its focus on parasite biology and mosquito-stage development relevant to malaria transmission pathways.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 6 auditable classifier relationships to diseases, places, topics, and study design.