Fungi Join the Fight Against Malaria

SLAP. You’re sitting outside at a summer bonfire and you catch a mosquito feasting on your leg. Groaning, you realize this probably means a couple days of itching and a swollen welt. Usually in North Carolina, you’re going to be just fine and should only seek medical attention if you experience complications. However, for many, particularly in Sub-Saharan Africa, a mosquito bite can mean something particularly dangerous: the possibility of infection with malaria.

Cells infected with Plasmodium falciparum possess characteristic purple dots, often connected in a “headphones” shape. Source: Steven Glenn, Laboratory and Consultation Division, USCDCP (PIXIO)

Malaria is a parasitic infection caused by Plasmodium falciparum, a single-celled organism that lives in the salivary gland of Aedes aegypti mosquitoes and is considered the deadliest human parasite. The World Health Organization reported in 2018 that progress in reducing cases of malaria globally has stalled, with nearly 435,000 people, primarily Sub-Saharan African children, dying from the disease per year. Much of this lack of progress can be attributed to mosquitoes developing a tolerance for commonly used chemical insecticides. Recent work from scientists at the University of Maryland in collaboration with researchers in Burkina Faso has hacked biology to create a new tool to combat the problem of malaria-carrying mosquitoes. The tool? Genetically modified fungus that wipes out mosquitoes with a deadly dose of spider toxin.

To develop their tool, the researchers used a type of fungus that already occurs in malaria-affected areas and targets mosquitoes: Metarhizium pingshaense. This species of fungus is entomopathogenic, which means that the fungus is a parasite to insect hosts and kills or disables them. In the wild, this fungus can kill mosquitoes, albeit quite slowly. It takes over a week in the lab for Metarhizium to kill a mosquito, by which time the mosquito could spread malaria and reproduce. To speed up the process, the scientists used genetic engineering to give Metarhizium a deadly tool: a gene from the Australian Blue Mountains Funnel-web spider that creates a potent toxin. In the wild, the spider’s fangs deliver a neurotoxin that disrupts the way neurons send signals in the brain. This causes symptoms including dangerously elevated heart rate and blood pressure and difficulty breathing. If bitten by a funnel web spider, death can occur in humans rapidly. However, to ensure the toxin only affects mosquitos, the scientists disabled the toxin from being made by the fungus until the right moment — when the fungus reaches the bloodstream of the mosquito.

The Australian Funnel Web spider is considered to be one of the deadliest spiders on Earth. Source: Brenda Clarke (flickr)
A cockroach infected with a species of Metarhizium. Source: Chengshu Wang and Yuxian Xia, PLoS Genetics Jan. 2011 (Wikimedia Creative Commons)

The fungus was tested in a unique environment in Burkina Faso: the MosquitoSphere, an enclosure where genetically modified organisms are permitted to be tested.

To conduct the experiment, two populations of 1500 mosquitoes were released in the MosquitoSphere. To expose the insects to the fungus, the investigators mixed the Metarhizium spores with sesame oil and spread the mixture onto black cotton sheets. When mosquitoes landed on the sheets, they were exposed to the toxic fungal spores. The mosquito population exposed to the unmodified Metarhizium had no problem reproducing before the fungus proved fatal, with their population totaling nearly 2500 after 45 days. In contrast, the population of mosquitoes exposed to the genetically modified Metarhizium after 45 days shrunk to a mere 13 individuals. A population of 13 mosquitoes indicated that the mosquitoes were dying more quickly than they could breed, therefore producing an unsustainable, or collapsed population. The striking results of the experiments in the MosquitoSphere encouraged the investigators to conclude that the genetically modified Metarhizium can function as a potent mosquito-killing bio-pesticide and cause an interbreeding colony of mosquitoes to collapse in a little over a month.

Despite success in the MosquitoSphere, the fungus still needs to undergo more testing to be considered safe for humans and the environment. If it is approved, a formulation of the fungal spores could be used to protect dwellings and mosquito netting from malaria-carrying mosquitoes. This study is a promising sign for the use of genetically modified bio-pesticides to wipe out disease-causing insects, which could prove invaluable for malaria prevention. 

Peer editor: Elise Hickman

In the Wake of Hurricane Florence: How Genetic Tools Can Prevent Ecosystem Damage

Hurricane Florence approaches the Carolinas

Hurricane Florence was devastating to much of the Carolinas. The flooding that ensued destroyed not only homes and livelihoods, but greatly affected animal agriculture. The effects of Florence resulted in the deaths of millions of animals and caused massive overflows or “overtopping” of animal waste, particularly from swine production facilities. North Carolina is the nation’s second largest producer of swine, and the 9.7 million pigs who call North Carolina home produce nearly 10 billion gallons of waste annually. The damages from Florence are disastrous not only from an economic perspective, but also from an environmental one.

In livestock production, lagoons are large basins primarily used for the treatment of animal wastes. Rather than simply being a collection site for waste, proper care of a lagoon involves “feeding” the lagoon with microbes that help degrade the waste into usable fertilizer. However, during massive flooding events the volume within these lagoons can quickly rise and overflow. This disrupts the waste treatment process and exposes the environment to large quantities of nitrogen, phosphorus, or even pathogenic material derived from animal wastes. According to the North Carolina Department of Environmental Quality, at least 32 lagoons have overtopped due to Florence, and another 61 lagoons have sustained structural damage or are close to overflowing.

An imbalance of nitrogen and phosphorus in any body of water contributes to a condition called eutrophication, in which excess nutrients allow for blooms of algae or plant matter. As these photosynthetic organisms flourish, they cause drastic changes to their environment. Algal blooms can be especially damaging, as many algae produce compounds which quickly reach toxic levels, algal overabundance clouds the water, and their rapid growth utilizes carbon leading to an increase in the pH of surrounding water. Eventually, algae change their own environment so extensively that they quickly die off, leading to subsequent microbial breakdown of the dead algae, which depletes oxygen. This rapid removal of oxygen then produces a “dead zone”, which is unsustainable for most life.

While nitrogen and phosphorus can be detrimental to the environment in large quantities, these are still very necessary components of any animal’s diet. Nitrogen and phosphorus are used as building blocks to produce DNA, proteins, and other compounds necessary for the growth. Therefore, agricultural production will need to find ways to provide these necessary building blocks while also preventing an excess of them in the environment. Thankfully, animal science research efforts have produced a unique potential fix!

Several years ago, researchers at the University of Guelph in Canada developed an animal designed with the world in mind: the Enviropig! The Enviropig is a transgenic animal, meaning its genome has been edited to contain a gene from a different species. In the case of the Enviropig, a bacterial-derived gene for the enzyme phytase is expressed in the pigs’ salivary glands, allowing the animal to break down more of the phosphorus in its diet. With more phosphorus broken down into a form the animal can digest, less phosphorus winds up in pigs’ waste, meaning less phosphorus contributes to eutrophication. A win for the pigs, now able to get better nutrition from their diet, and a win for humans and the environment, as we are able to produce and enjoy a more environmentally sustainable product. While the initial work on this project was put on hold in 2012 due to public scrutiny of genetically modified organisms (GMOs), a team of researchers in China developed their own version of an environmentally-conscious pig earlier this year. This new animal is able to break down greater amounts of both phosphorus and nitrogen from its diet, reducing their abundance in animal wastes.

Neither animal has been approved for use in the United States yet, but they both hold enormous potential to reduce the environmental impacts of animal agriculture. While the Enviropig and similar transgenic animals cannot yet solve every environmental issue, had they been mainstream prior to Hurricane Florence, perhaps there would be less concern with regard to ecosystem health after the flooding. Natural disasters are as unpredictable as they are unfortunate and dangerous; however, genetic tools such as these could provide one additional safeguard to protect the environment and public safety for the future.

Livestock, such as pigs, can be genetically designed to help protect the environment!

Peer edited by Joanna Warren.

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