Exposure to L-cycloserine incurs survival costs and behavioral alterations in Aedes aegypti females

Abstract

Background: It was previously demonstrated that alanine aminotransferase (ALAT, EC 2.6.1.2) participates in maintaining the alanine-proline cycle between flight muscles and fat body during Aedes aegypti flight. ALAT is also actively involved in the metabolism of ammonia in A. aegypti. Here, we investigated the survival and behavioral costs of ALAT inhibition in A. aegypti females to better understand the role of ALAT in blood-fed mosquitoes. Methods. We analyzed how A. aegypti female mosquitoes respond to blood meals supplemented with 0, 2.5, 5 and 10 mM L-cycloserine, a well-known inhibitor of ALAT in animals. Mosquitoes were also exposed to blood meals supplemented with L-cycloserine and different concentrations of glucose (0, 10 and 100 mM). Additionally, the effects of ALAT inhibitor and glucose in mosquitoes starved for 24 or 48 h were investigated. Survival and behavioral phenotypes were analyzed during a time course (1, 2, 4, 6, 12, 24, 48 and 72 h after feeding). Results: L-cycloserine at 10 mM resulted in high mortality relative to control, with an acute effect during the first 6 h after treatment. A significant decrease in the number of active mosquitoes coinciding with an increase in futile wing fanning during the first 24 h was observed at all inhibitor concentrations. A high occurrence of knockdown phenotype was also recorded at this time for both 5 and 10 mM L-cycloserine. The supplementation of glucose in the blood meal amplified the effects of the ALAT inhibitor. In particular, we observed a higher mortality rate concomitant with an increase in the knockdown phenotype. Starvation prior to blood feeding also increased the effects of L-cycloserine with a rapid increase in mortality. Conclusions: Our results provide evidence that exposure of high doses of L-cycloserine during A. aegypti blood feeding affects mosquito survival and motor activity, suggesting an interference with carbohydrate and ammonia metabolism in a time-dependent manner.