Bacterium Disrupts Malaria Parasite Development in Mosquitos

Mosquito photo

Mosquitos are the deadliest animal on earth—not because of the itchy bites they leave behind, but because of the diseases those bites can spread. Of these diseases, malaria, is the most widespread, killing 619,000 people in 2021 (1). Almost half of the world’s population live at risk of malaria (2). In humans, malaria is caused by certain species of single-cell micro-organisms belonging to the genus Plasmodium (3), which are transmitted by anopheline mosquitos.

Controlling malaria has proven challenging. Vaccines have yielded incomplete protection, and insecticides that once were successful at control mosquito populations are becoming less effective as the insects develop resistance. Finally, Plasmodium parasites themselves have developed resistance to leading anti-malaria drugs (2).

A New Weapon In The Fight Against Malaria

Approaches that target the disease-causing Plasmodium organisms—inside the mosquito and before they are transmitted to humans—could provide as effective way forward. In the past, researchers have explored leveraging genetically modified bacterium to kill or inhibit Plasmodium development within their mosquito host. However, using genetically altered bacteria makes wide-spread adoption of these techniques problematic. A recent study published in Science describes the discovery and early investigative results using a naturally occurring bacterial strain that inhibits Plasmodium spread (2). The bacteria, Delftia tsuruhatensis TC1, was isolated from a mosquito population that unexpectedly became resistant to Plasmodium infection (2).

Image courtesy of James Gathany and the CDC

Once the bacterium was identified as the cause of Plasmodium inhibition, the researchers tested how easily the bacteria was to introduce into naïve mosquitos and how effective it was at disrupting infection. To do this, they colonized female mosquitos by feeding them a sugar and bacterium solution and then Plasmodium-infected blood. Bacterial colonization occurred in almost all the mosquitos offered the sugar and bacterium food. Initially, bacterial colonization numbers were low, but they increased 100-fold following the blood meal.

Inhibiting Oocyte Formation Disrupts Cycle of Infection

Investigation into how D. tsuruhatensis inhibits Plasmodium infection showed that it inhibits oocyte formation within the gut, and this inhibition lasts for at least 16 days. Specifically, the inhibition is the result of a secreted compound called harmane, which is a small hydrophobic methylated b-carboline (2). When harmane is secreted in the guts of mosquitos it inhibits Plasmodium parasite development. The researchers further found that feeding harmane alone to mosquitos, or allowing it to be absorbed through direct contact produced the same results, but the inhibitory effects only lasted a few days (2).

No matter how harmane is introduced into the gut (directly or through bacterial colonization), the inhibition of oocyte formation results in a decrease in infectivity. Only one third (33%) of mice bitten by Plasmodium-infected, D. tsuruhatensis-colonized mosquitos become infected. This contrasts sharply with the 100% infection rate seen with mice bitten by non-colonized, Plasmodium-infected mosquitos (2). Further testing the researchers also showed that D. tsuruhatensis is not transferred during feeding, suggesting that that bacterium is unlikely to in introduced into mammals through colonized mosquitos.

To investigate how colonization and infection rates would correlate in a ‘real world’ environment, the researchers used a large (10 × 10 × 5 meter) enclosure that replicated the mosquitos’ natural environment. Once again, the mosquitos were colonized with D. tsuruhatensis through overnight feeding of the sugar and bacterium solution. They found ~75% of the mosquitos were colonized by D. tsuruhatensis in this time period.They also found that larvae reared in water seeded with D. tsuruhatensis experienced 100% colonization. In both scenarios, Plasmodium oocyte development was disrupted just as it had been in the laboratory-raise population (2).

Finally, the researchers found that D. tsuruhatensis colonization doesn’t occur between individuals between parent and offspring. For controlling Plasmodium, this means that inoculation with D. tsuruhatensis would require ongoing maintenance. However, it also decreases the risk of a contaminated strain being amplified uncontrollably if released, making it less risky.

Malaria mitigation and control requires a multipronged effort. Using naturally occurring, symbiotic, microbes such as D. tsuruhatensis is one approach that shows promise. There is still a lot of work to be done before this bacterium could be used outside of a controlled environment, including understanding how the bacterium might interact with other plants and animals from the same ecosystem.


  1. WHO World malaria report 2022.  Accessed August 22, 2023
  2. Wei Huang et al. (2023) Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes. Science 381, 533–40.
  3. Website. CDC about Malaria—Biology. Accessed August 22, 2023

How Promega Helped Our Lab Scale Up Drug Discovery for Bloodborne Pathogens

This blog was written by Sebastien Smick, Research Technician in Dr. Jacquin Niles’ laboratory at Massachusetts Institute of Technology (MIT)

Our lab is heavily focused on the basic biology and drug discovery of the human bloodborne pathogen Plasmodium falciparum, which causes malaria. We use the CRISPR/Cas9 system, paired with a TetR protein fused to a native translational repressor alongside a Renilla luciferase reporter gene, to conditionally knock down genes of interest to create modified parasites. We can then test all kinds of compounds as potential drug scaffolds against these gene-edited parasites. Our most recent endeavor, one made possible by Promega, is a medium-low throughput robotic screening pipeline which compares conditionally-activated or-repressed parasites against our dose-response drug libraries in a 384-well format. This process has been developed over the past few years and is a major upgrade for our lab in terms of data production. Our researchers are working very hard to generate new modified parasites to test. Our robots and plate readers rarely get a day’s rest!

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Firefly Luciferase Sheds Light on Development of New Malaria Treatments

field of fireflies at night; researchers are using firefly luciferase as a tool to power screening assays for new malaria treatments

Despite significant advancements in antimalarial drugs and widespread efforts to prevent transmission over the past decade, deaths from malaria remain high, particularly in younger children. New drugs with novel modes of action are urgently needed to continue reducing mortality and address drug resistance in the malaria parasite, Plasmodium falciparum. While tens of thousands of compounds have been identified as potential candidates through massive screening efforts, scalable methods for identifying the most effective compounds are needed.

The goal is to find a drug that is potent during all stages in the life cycle of P. falciparum and kills the parasite quickly. Focusing on assessing whether a compound can rapidly eliminate initial parasite burden, Paul Horrocks, PhD, and his colleagues developed a validated bioluminescence-based assay that rapidly determines the initial rate of kill for discovery antimalarials. One key to developing their assay was figuring out how to monitor when the parasite dies after introducing the drug. While measuring DNA content can be used to monitor parasite burden, it is too stable to use for a relevant time course assay.

See how Dr. Paul Horrocks uses a firefly luciferase-based system to understand the dynamics of drug action in the development of new malaria treatments.

Enter firefly luciferase, a dynamic reporter tool to investigate drug action. By creating transgenic P. falciparum that express the luc reporter gene, the researchers could monitor drug action over time. When the parasite is killed, it stops making the luciferase reporter. Since there is no new production of luciferase, levels fall quickly after the parasite dies, and a luciferase assay can determine how fast each drug killed the parasite.

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How Do You Solve a Problem Like Malaria?

Photo courtesy of NIH/NIAID

Malaria affects nearly half of the world’s population, with almost 80% of cases in sub-Saharan Africa and India. While there have been many strides in education and prevention campaigns over the last 30 years, there were over 200 million cases documented in 2017 with over 400,000 deaths, and the majority were young children. Despite being preventable and treatable, malaria continues to thrive in areas that are high risk for transmission. Recently, clinicians started rolling out use of the first approved vaccine, though clinical trials showed it is only about 30% effective. Meanwhile, researchers must continue to focus on innovative efforts to improve diagnostics, treatment and prevention to reduce the burden in these areas.

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Chikungunya Virus and the Promise of a Virus-Like Particle Vaccine

My family and I just returned from a week-long camping trip along the North Shore of Lake Superior in Minnesota. It is beautiful country, filled with lakes, rivers, ponds—and mosquitoes, lots and lots of mosquitoes. We went prepared for the worse. We had a screen tent, head nets and tubes and tubes of insect repellent because in this area of the world, mosquitoes are a flying, buzzing, picnic-ruining, itch-inducing pest. In the US, though, a pest is really all they are. In other areas of the world they are a flying, buzzing, disease-carrying, deadly menace.

Image courtesy of James Gathany and the CDC
Image courtesy of James Gathany and the CDC

Mosquitos act as vectors for many diseases including malaria, Dengue fever, Yellow fever, encephalitis, West Nile Virus and chikungunya virus. Many of these diseases are deadly; in fact, mosquitoes are responsible for more human deaths than any other animal (~725,000 deaths annually). Although most of these diseases have a long and infamous history, two of them, West Nile virus (first identified in 1932) and chikungunya virus (first identified in 1950), are relative new comers on the world health stage. Continue reading “Chikungunya Virus and the Promise of a Virus-Like Particle Vaccine”

Genetically Modified Mosquitoes Fight Malaria

Image courtesy of James Gathany and the CDC
Image courtesy of James Gathany and the CDC

Mosquitos: They are the scourge of summer activities—the annoying buzzing noise as they fly around our ears and the pain, itching and swelling associated with their bites. Worst of all, certain species of mosquitoes can transmit diseases such as West Nile virus, Dengue fever and malaria. Defense mechanisms such as mosquito repellent, covering my head with netting and wearing heavy clothing are often insufficient against the swarm of hungry insects. It’s enough to make me want to stay indoors.

Those people who cannot escape these pests have a higher risk of being bitten and contracting a disease such as malaria, which killed an estimated 627,000 people in 2012, mostly in Africa and southeast Asia (1). A common step in malaria reduction programs in high-risk areas is reducing the number of Anopheles gambiae mosquitoes, which act as the host for malaria-causing parasites. This often involves massive amounts of insecticides, including limited amounts of the much maligned but very effective insecticide dichlorodiphenyltrichloroethane (DDT). Due to these programs, the World Health Organization (WHO) estimates that between 2000 and 2012, malaria mortality rates decreased by 42% worldwide, including a 48% decrease in children under 5 years of age. Clearly these programs are saving lives, but wouldn’t it be nice to achieve the same thing with fewer pesticides?

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