Tag: mosquito-borne diseases

Scientists Abuzz over a Genetic Way to Deafen Mosquitoes

Photo by Ekamelev on Unsplash

Specific receptors in the ears of mosquitoes have been revealed to modulate their hearing, finds a new study led by researchers at UCL and University of Oldenburg. Since male mosquitoes need to hear female mosquitoes is a crucial factor in their reproduction, this discovery could help develop new insecticides and control the spread of harmful diseases, such as malaria, dengue, and yellow fever.

In the study, published in Nature Communications, the researchers focused on a signalling pathway involving a molecule called octopamine. They demonstrated that it is key for mosquito hearing and mating partner detection, and so is a potential new target for mosquito control.

Male mosquitoes acoustically detect the buzz generated by females within large swarms that form transiently at dusk.

As swarms are potentially noisy, mosquitoes have developed highly sophisticated ears to detect the faint flight tone of females amid hundreds of mosquitoes flying together.

However, the molecular mechanisms by which mosquito males ‘sharpen their ears’ to respond to female flight tones during swarm time have been largely unknown.

The researchers looked at the expression of genes in the mosquito ear and found that an octopamine receptor specifically peaks in the male mosquito ear when mosquitoes swarm.

The study found that octopamine affects mosquito hearing on multiple levels. It modulates the frequency tuning and stiffness of the sound receiver in the male ear, and also controls other mechanical changes to boost the detection of the female.

The researchers demonstrated that the octopaminergic system in the mosquito ear can be targeted by insecticides. Mosquito mating is a bottleneck for mosquito survival, so identifying new targets to disrupt it is key to controlling disease-transmitting mosquito populations.

Source: University College London

Inflammation Impedes the Development of Malaria Parasites

Photo by Ekamelev on Unsplash

Researchers have found that inflammation can slow down the development of malaria parasites in the bloodstream, which may lead to a new strategy for preventing or limiting severe disease.

The malaria-causing Plasmodium parasites invade and multiply within red blood cells. Studies have shown that the parasites can rapidly sense and respond to conditions within the host by intimately syncing with their internal body clocks. While it is known that the body’s nutrient levels and daily circadian rhythms affect the parasites’ development, little was known about the impact of host inflammation on the parasites.

This animal-model study, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Kirby Institute and published in the journal mBio, reveals that when the body’s immune system responds to inflammation it alters the plasma’s chemical composition, directly impeding the maturation of the Plasmodium parasites in the bloodstream.

University of Melbourne’s Associate Professor Ashraful Haque, a senior author of the paper, said this work highlights the captivating dynamic of the host-parasite relationship.

“First, we discovered that inflammation in the body prevented the early stage of the parasites from maturing. We also noticed that inflammation triggered significant changes in the composition of the plasma – we were actually quite surprised by the magnitude of these changes,” said Associate Professor Haque.

“As we dug deeper, we found substances in the altered plasma that, we believe, are what may inhibit parasite growth in the body. This work reveals a new mechanism that slows down the malaria parasite’s development in the bloodstream. Our research was done using animal models, so it would be really interesting to study if such inhibitory mechanisms occur in humans too.”

Dr David Khoury, co-senior author of the paper, said the scientists found a remarkable response by the parasites to the changes in their environment.

“Parasites residing in red blood cells rapidly sense and respond to their new environment, showing fascinating adaptability. Using cutting-edge genome sequencing technology, we observed that even after just four hours in this changed plasma, the parasites adjusted their genetic and protein activity, resulting in slower maturation within red blood cells. It’s almost like the parasites actively sense an inhospitable host environment, and as a result trigger a coping mechanism,” said Dr Khoury.

“We believe this is the first study to show that inflammation can change how individual parasites behave genetically in the body.”

Professor Miles Davenport, co-senior author of the paper, said this work on the interaction between systemic host inflammation and malaria parasite maturation offers several potential benefits.

“This study, while based on animal models, broadens our understanding of malaria. It provides a foundation for further investigations into the specific mechanisms involved in the modulation of parasite maturation by inflammation, and opens avenues for future studies to explore the identified inhibitory factors, genetic changes and their implications for malaria development,” said Professor Davenport.

Source: The Peter Doherty Institute for Infection and Immunity

A New Mosquito Repellent Alternative to DEET

Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

The chemical DEET has proven effective at keeping disease-carrying mosquitoes at bay, but the repellent is smelly and its protection is short-lived. Now, researchers report in the Journal of Agricultural and Food Chemistry that they have designed safe alternatives with some advantages over DEET, including a nice smell and much longer protection.

DEET disrupts a mosquito’s ability to locate humans. Until recently, it was considered the gold standard among topical repellents, but some find its strong odor offensive. It has to be reapplied frequently, and at high concentrations, it can damage synthetic fabrics and plastics. Another popular repellent known as picaridin is now regarded as a better alternative, since its protective effect lasts longer, and it doesn’t have an odor or damage items. However, like DEET, it has to be reapplied after swimming or sweating.

So, Francesca Dani and colleagues wanted to look for alternatives to these established products. In prior work, the team used as starting materials two plant-based natural repellents that offered only short-term protection from mosquitoes. The researchers converted these terpenoids into cyclic acetals and hydroxyacetals, thereby extending their protective timespan beyond that of DEET. But the researchers wanted to improve on these initial products.

In the current work, the team synthesised additional cyclic hydroxyacetals from inexpensive, commercially available carbonyls. The new cyclic compounds had pleasant, much fainter odors and were easier to dissolve in water, meaning they can be formulated without high concentrations of alcohol. Some were as effective as DEET and picaridin at repelling Asian tiger mosquitoes, which have spread widely in the U.S. and carry diseases, including encephalitis, dengue and dog heartworm. And like picaridin, they provided human volunteers more than 95% protection from bites for at least eight hours, while DEET’s protection rapidly declined below that level after just two hours.

Toxicity of some of the most active new compounds was comparable to or lower than the traditional repellents. Two hydroxyacetals were also less likely to cause immune reactions or to penetrate cell layers than picaridin. The researchers conclude that their compounds represent a new class of promising mosquito repellents that can compete favorably with DEET and picaridin in terms of efficacy and safety.

Source: American Chemical Society

Gene Drive to Control Mosquito-borne Disease a Step Closer

Image source: Ekamalev at Unsplash

Scientists have developed a set of tools that will help create a gene drive to control mosquito-borne diseases such as the West Nile virus, which has received less attention than controlling mosquitoes that transmit malaria.

Since the advent of CRISPR genetic editing revolution, scientists have been working to use the technology to develop gene drives that target pathogen-spreading mosquitoes such as Anopheles and Aedes species, which spread malaria, dengue and other life-threatening diseases.

Much less genetic engineering work has focused on Culex genus mosquitoes, which spread devastating afflictions stemming from West Nile virus, as well as other viruses such as the Japanese encephalitis virus (JEV). Culex mosquitoes are a significant health risk in Africa and Asia, where they transmit the worm causing filariasis, a disease that can lead to a chronic debilitating condition known as elephantiasis.

University of California San Diego scientists have now developed a number of genetic editing tools that will help create a gene drive designed to stop Culex mosquitoes from spreading disease. Gene drives are designed to spread modified genes, in this case those that disable the ability to transmit pathogens, throughout the targeted wild population. The new study is published in the journal Nature Communications,

The researchers developed a Cas9/guide-RNA expression ‘toolkit’ designed for Culex mosquitoes. Since so little genetic engineering work has been done on Culex mosquitoes, the researchers were required to develop their toolkit from scratch, starting with a careful examination of the Culex genome.

“My coauthors and I believe that our work will be impactful for scientists working on the biology of the Culex disease vector since new genetic tools are deeply needed in this field,” said Gantz, an assistant research scientist in the Division of Biological Sciences at UC San Diego. “We also believe the scientific community beyond the gene drive field will welcome these findings since they could be of broad interest.”

The researchers also demonstrated the applicability of their tools in other insects.

“These modified gRNAs can increase gene drive performance in the fruit fly and could potentially offer better alternatives for future gene drive and gene-editing products in other species,” said Gantz.

Gantz and his colleagues have now tested their new tools to ensure proper genetic expression of the CRISPR components and are now on the verge of applying them to a gene drive in Culex mosquitoes. This could be used to stop pathogen transmission by Culex mosquitoes, or alternatively employed to suppress the mosquito population to prevent biting.

Source: University of California San Diego