AUTHOR=Kwon Hyeogsun , Smith Ryan 

TITLE=Anopheles gambiae Actively Metabolizes Uric Acid Following Plasmodium Infection to Limit Malaria Parasite Survival

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.821869

DOI=10.3389/fphys.2021.821869

ISSN=1664-042X

ABSTRACT=<p>Characterizing the physiological changes that accompany malaria parasite infection of the mosquito host is crucial to our understanding of vectorial capacity in <italic>Anopheles</italic> mosquitoes, yet has not fully been explored. In this study, we examine the role of uric acid metabolism in the mosquito, <italic>Anopheles gambiae</italic>, following malaria parasite infection. We demonstrate that levels of uric acid are significantly decreased in the excreta and the mosquito at 24 and 48 h post-<italic>Plasmodium</italic> infection when compared to controls fed on naïve mouse blood. When we examine the expression of well-known enzymes responsible for uric acid metabolism, we see a significant increase in both <italic>urate oxidase</italic> (<italic>UO</italic>) and <italic>allatoicase</italic> (<italic>ALLC</italic>) expression following <italic>Plasmodium</italic> infection. Targeting the essential first step in uric acid metabolism by silencing <italic>UO</italic> resulted in elevated levels of uric acid, enhancing malaria parasite survival. With implications from other insect systems that bacteria can modulate UO expression, we examined the possibility that the mosquito microbiota and its expansion following blood-feeding may contribute to increased UO levels. However, there was no difference in uric acid metabolism between septic and aseptic mosquitoes, indicating that the mosquito microbiome is not associated with the manipulation of <italic>UO</italic> expression. Together, our study provides new evidence that <italic>Plasmodium</italic> infection causes the mosquito host to actively metabolize uric acid by increasing <italic>UO</italic> expression to limit <italic>Plasmodium</italic> oocyst survival, suggesting that nitrogen metabolism is an essential pathway in defining mosquito vector competence.</p>