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Low levels of reactive oxygen species (ROS) are now recognized as essential players in cell signaling. Here, we studied the role of two conserved enzymes involved in redox regulation that play a critical role in the control of ROS in the digestive physiology of a blood-sucking insect, the kissing bug  Rhodnius prolixus . RNAi-mediated silencing of  RpNOX5  and  RpXDH  induced early mortality in adult females after a blood meal. Recently, a role for  RpNOX5  in gut motility was reported, and here, we show that midgut peristalsis is also under the control of  RpXDH . Together with impaired peristalsis, silencing either genes impaired egg production and hemoglobin digestion, and decreased hemolymph urate titers. Ultrastructurally, the silencing of  RpNOX5  or  RpXDH  affected midgut cells, changing the cells of blood-fed insects to a phenotype resembling the cells of unfed insects, suggesting that these genes work together in the control of blood digestion. Injection of either allopurinol (an XDH inhibitor) or uricase recapitulated the gene silencing effects, suggesting that urate itself is involved in the control of blood digestion. The silencing of each of these genes influenced the expression of the other gene in a complex way both in the unfed state and after a blood meal, revealing signaling crosstalk between them that influences redox metabolism and nitrogen excretion and plays a central role in the control of digestive physiology.

“Urate and NOX5 Control Blood Digestion in the Hematophagous Insect Rhodnius prolixus”