Malpighian Tubules as Novel Targets for Mosquito Control

Abstract

The Malpighian tubules and hindgut are the renal excretory tissues of mosquitoes; they are essential to maintaining hemolymph water and solute homeostasis. Moreover, they make important contributions to detoxifying metabolic wastes and xenobiotics in the hemolymph. We have focused on elucidating the molecular mechanisms of Malpighian tubule function in adult female mosquitoes and developing chemical tools as prototypes for next-generation mosquitocides that would act via a novel mechanism of action (i.e., renal failure). To date, we have targeted inward rectifier potassium (Kir) channels expressed in the Malpighian tubules of the yellow fever mosquito Aedes aegypti and malaria mosquito Anopheles gambiae. Inhibition of these channels with small molecules inhibits transepithelial K+ and fluid secretion in Malpighian tubules, leading to a disruption of hemolymph K+ and fluid homeostasis in adult female mosquitoes. In addition, we have used next-generation sequencing to characterize the transcriptome of Malpighian tubules in the Asian tiger mosquito Aedes albopictus, before and after blood meals, to reveal new molecular targets for potentially disrupting Malpighian tubule function. Within 24 h after a blood meal, the Malpighian tubules enhance the mRNA expression of genes encoding mechanisms involved with the detoxification of metabolic wastes produced during blood digestion (e.g., heme, NH3, reactive oxygen species). The development of chemical tools targeting these molecular mechanisms in Malpighian tubules may offer a promising avenue for the development of mosquitocides that are highly-selective against hematophagous females, which are the only life stage that transmits pathogens.

Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes

“…Malpighian tubules have been suggested as a novel target for mosquito control via mosquitocides that specifically target renal function in hematophagous females (49). Our work suggests that they could also be a target for control through a tissue-specific expression system targeting immune up-regulation.…”

Identification and Expression of Inward-Rectifying Potassium Channel Subunits in Plutella xylostella

“…The expression and function of Kir subunits in D. melanogaster, A. aegypti, and N. lugens have been reported: Kir subunits are expressed in the insects' Malpighian tubules [17,22,25,26], CNS [46], muscle [30], salivary glands [19,29], and reproductive organs [24], where they regulate the insects' renal function, heart function, patterning, salivary gland function, and virus resistance. This study also investigated the expression of Kir subunits in the CNS (head), digestion and metabolite excretion organs (midgut and Malpighian tubules), locomotive organs (thorax, legs, wings), and reproductive organs (ovarian tubule and testis) of P. xylostella.…”

“…kir1 is highly expressed during the pupal stage and in Malpighian tubules in adults, and the kir1 is highest expressed in the ovarian tubule of A. gambiae [19,21,24,25]. kir2 and kir3 are also highly expressed in Malpighian tubules [15,19,20,22,26]. In A. gambiae, kir2 has three subclasses and kir3 has two subclasses [17,18,22].…”

Mosquito-Borne Diseases and Omics: Tissue-Restricted Expression and Alternative Splicing Revealed by Transcriptome Profiling of Anopheles stephensi

“…Fat body and ovary are known to be involved in the utilization of the nutrients from blood to enable vitellogenesis. Malpighian tubules along with the hindgut form the excretory system of the mosquitoes and are known to be rich in the solute transporters (Dow, 2009;Piermarini et al, 2017).…”

“…Fat body cells (trophoblasts) and Malpighian tubules have also been shown to be involved in the immune responses (Dow, 2009;Martins et al, 2011;Piermarini et al, 2017;Verma and Tapadia, 2012). Therefore, these organs are now being considered as targets for mosquito control (Dow, 2009;Piermarini et al, 2017). Toward this end, we further evaluated the expression of An.…”