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The role of PbAP2-L and PbAP2-HC transcription factors and reticulocytes in Plasmodium nutrient sensing
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Orientador(es)
Resumo(s)
Malaria is a life-threatening tropical disease caused by Plasmodium spp., an obligatory intracellular parasite, transmitted via the bite of an infected mosquito. Once in the host´s system, it undergoes two infection stages, the liver stage followed by the blood stage, both of which have high replication rates. Additionally, Plasmodium also has a very complex life cycle, having the necessity to adapt to different niches, indicating strict control over its gene expression and high nutritional demands. Plasmodium nutrition is dependent on the host, as it retrieves nutrients from the host´s system. While most eukaryotes possess AMPK and TOR as nutrient-sensing mechanisms, Plasmodium possesses KIN, a kinase related to AMPK/SNF-1, whose pathway is not well-known in Plasmodium but can influence gene expression under calorie restriction. Once active, KIN leads to a decrease in Plasmodium blood stage replication and higher survival rates in Plasmodium-infected mice. As transcription factors (TFs) are involved in nutrient sensing in most eukaryotes, this study aimed to determine the involvement of two Plasmodium TFs, PbAP2-L, essential for liver stage development, and PbAP2-HC, not essential for any stage of parasite, in nutrient-sensing under Calorie Restriction (CR) by infecting Balb/c mice under a CR diet with P. berghei knockout lines for PbAP2-L and PbAP2-HC. We determined that these TFs were not involved in nutrient-sensing under in vivo CR, contrary to previous in vitro findings. We established that CR mice must lose 20% of their body weight before P. berghei infection, for the parasites to reduce replication in response to CR. Furthermore, it was also observed that during infection, CR mice had higher reticulocytemia than Ad Libitum (AL) mice, which could contribute to the protective effect against severe malaria, as parasite´s replication seems to be reduced in reticulocytes during CR conditions.
Descrição
Tese de mestrado, Microbiologia Aplicada, 2026, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
calorie restriction PbAP2-L PbAP2-HC Plasmodium berghei nutrient sensing