AUTHOR=Ukegbu Chiamaka V. , Christophides George K. , Vlachou Dina 

TITLE=Identification of Three Novel Plasmodium Factors Involved in Ookinete to Oocyst Developmental Transition

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.634273

DOI=10.3389/fcimb.2021.634273

ISSN=2235-2988

ABSTRACT=<p><italic>Plasmodium falciparum</italic> malaria remains a major cause of global morbidity and mortality, mainly in sub-Saharan Africa. The numbers of new malaria cases and deaths have been stable in the last years despite intense efforts for disease elimination, highlighting the need for new approaches to stop disease transmission. Further understanding of the parasite transmission biology could provide a framework for the development of such approaches. We phenotypically and functionally characterized three novel genes, <italic>PIMMS01</italic>, <italic>PIMMS57</italic>, and <italic>PIMMS22</italic>, using targeted disruption of their orthologs in the rodent parasite <italic>Plasmodium berghei</italic>. <italic>PIMMS01</italic> and <italic>PIMMS57</italic> are specifically and highly expressed in ookinetes, while <italic>PIMMS22</italic> transcription starts already in gametocytes and peaks in sporozoites. All three genes show strong phenotypes associated with the ookinete to oocyst transition, as their disruption leads to very low numbers of oocysts and complete abolishment of transmission. <italic>PIMMS22</italic> has a secondary essential function in the oocyst. Our results enrich the molecular understanding of the parasite-vector interactions and identify <italic>PIMMS01</italic>, <italic>PIMMS57</italic>, and <italic>PIMMS22</italic> as new targets of transmission blocking interventions.</p>