Xanthine dehydrogenase-1 silencing in Aedes aegypti mosquitoes promotes a blood feeding-induced adulticidal activity

Abstract

Aedes aegypti has 2 genes encoding xanthine dehydrogenase (XDH).We analyzed XDH1andXDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injectingdouble-strandedRNA(dsRNA) againstXDH1, XDH2, orboth.Disruption ofXDHby allopurinol orXDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, andreproduction.XDH1-deficientmosquitoes showedapersistenceof serineproteases inthemidgut at 48 h after blood feeding and a reduction in the uptake of vitellogenin by the ovaries. Surprisingly, analysis of the fat body from dsRNA-XDH1-injectedmosquitoes fell into 2 groups: one groupwas characterized by a reduction of the XDH1 transcript, whereas the other group was characterized by an up-regulation of several transcripts, including XDH1, glutamine synthetase, alanine aminotransferase, catalase, superoxide dismutase, ornithine decarboxylase, glutamate receptor, and ammonia transporter. Our data demonstrate that XDH1 plays an essential role and that XDH1has the potential to be used as ametabolic target for Ae. aegypti vector control.