WOOSTER, Ohio — Peter Piermarini believes there’s a new, biological way to combat the mosquitoes that transmit Zika, dengue, malaria and other dreaded diseases: make them unable to pee.
An entomologist with the College of Food, Agricultural, and Environmental Sciences at The Ohio State University, Piermarini and collaborators at Vanderbilt and Cornell universities are looking for ways to disrupt the mosquitoes’ Malpighian tubules, which are the equivalent of human kidneys.
“Female mosquitoes rely on their ‘kidneys’ when consuming a human blood meal,” Piermarini said. “They may ingest the equivalent of their own body mass in blood, so they need to immediately get rid of the excess fluid they consume. They achieve this by urinating on their host while they are still feeding.”
As a result, Piermarini explained, mosquitoes with impaired kidney function would be less likely to escape the human host they are feeding on and survive the ingestion of blood.
As part of this line of research, Piermarini’s team has previously identified a chemical that compromises a mosquito’s ability to excrete urine. This chemical, he said, interferes with the function of a class of mosquito proteins called potassium channels, which are involved in excretion.
“In addition to blocking their kidney function, the chemical leaves mosquitoes unable to fly and in several cases severely bloated, all of which would lead to a shorter lifespan for the mosquitoes.”
Additionally, in a new paper published earlier this year in the online journal PeerJ, Piermarini reported the discovery of 4,000 genes in the Malpighian tubules of the Asian tiger mosquito (Aedes albopictus), which are affected when the insect feeds on blood.
Aedes mosquitoes are responsible for the transmission of Zika virus, which can cause birth defects and poor pregnancy outcomes. They also help spread dengue fever, which infects hundreds of millions of people annually and can be fatal, and a host of other dangerous diseases worldwide.
Zika in Ohio
A highly invasive insect, the Asian tiger mosquito is present in parts of Ohio and could potentially transmit Zika if the virus were to become established in the state, according to Piermarini.
“Our data provide new insights into the molecular physiology of Malpighian tubules in mosquitoes,” Piermarini said, referring to the new study. “Our findings also reveal potentially important molecular targets for the development of chemical or gene-silencing insecticides that would disrupt renal function in mosquitoes.”
Piermarini said existing control measures for mosquitoes are being challenged by the emergence of resistance to conventional insecticides that target the mosquito nervous system. Consequently, he explained, it is becoming increasingly necessary to identify novel physiological targets to guide the development of new insecticides.
“We have demonstrated in our previous research that the ‘kidneys’ of mosquitoes offer a valuable, new physiological target for insecticides,” he said. “But our understanding of how this tissue contributes to the metabolic processing of blood meals by mosquitoes is limited.”
Genomics
To learn more about these processes, Piermarini and colleagues used state-of-the-art genomics to sequence the genes that are expressed in the Malpighian tubules of adult female Asian tiger mosquitoes, and documented the changes in gene expression that occur after mosquitoes feed on blood.
“We found significant changes in the expression of around 4,000 genes after blood feeding,” he said. “Notably, there was a suppression of genes associated with the production of urine and an activation of genes associated with the detoxification and excretion of metabolites produced during blood digestion.”
This study represents the first characterization of global gene expression in the Malpighian tubules of mosquitoes, and offers molecular insights into the physiological roles of the mosquito kidneys during the processing of blood meals.
“The results also demonstrate that blood feeding elicits a dramatic functional transition of the mosquito ‘kidney’ from a tissue specializing in urine production to one specializing in detoxification and metabolic waste excretion,” Piermarini explained.
With this information, Piermarini said, his team will now able to identify specific molecular mechanisms that may be playing especially important roles in the metabolism of blood meals by mosquito kidneys and would be high-priority targets for insecticide development.
“If we can develop insecticides targeting the mechanisms activated after a blood meal, then we may be able to establish next-generation mosquito-control products that are highly selective for adult female mosquitoes, which are the only blood-feeding life stage and are most important for disease transmission, and that would not be harmful to non-blood feeding beneficial insects, such as honeybees,” he said.
