Fruit fly opens doors to malaria research

Drosophila promising better understanding of a devastating human illness

One of sciences most familiar subjects, the fruit fly, now promises to help researchers better understand malaria, the devastating disease spread through mosquito bites.

Scientists at the National Institute of Allergy and Infectious Diseases (NIAID; Bethesda, MD) and the Whitehead Institute (Cambridge, MA) have for the first time grown malaria parasites in the fruit fly, creating an easily manipulated model for studying how the parasite develops in insects. Their research, reported in the current issue of Science, has already identified a part of the insect immune system that naturally attacks malaria parasites. The authors hope the new model will help identify factors critical to malaria transmission, and accelerate efforts to develop transmission-blocking vaccines and mosquitoes engineered to be parasite-resistant.

Malaria is a major global health problem and a high-priority research area within NIAID. The malaria parasite, Plasmodium, must cycle between humans and mosquitoes—specifically female mosquitoes of the species Anopheles, to spread within a population. When the mosquito bites an infected person, the insect can ingest the parasites present in the blood. Once inside the mosquito's digestive tract, the parasite reproduces and moves into the body cavity. There it passes through several different life stages before traveling to the insect's salivary glands, where it is released into the blood of another person when the mosquito bites again.

"Plasmodium is not a simple organism like a bacterium or virus," says Mohammed Shahabuddin, an investigator in NIAID's Laboratory of Parasitic Diseases and co-author of the paper. "It has multiple developmental forms, each of which is distinct from the other. One form causes disease in humans, another is swallowed by mosquitoes, still another form reproduces, others move through the insect's intestines, and yet another enters the salivary gland of the mosquito and infects people."

Studying how the parasite interacts with its insect host is difficult, he explains, because the mosquito's biochemical and genetic makeup are not well defined. Enter Drosophilia. "Our ability to grow Plasmodium in the fruit fly is especially fortunate because scientists recently determined the complete sequence of the Drosophila genome. So now we can scan the entire genome and identify the specific genes involved in the fruit fly's response to Plasmodium, and then look for the corresponding genes in the mosquito."

Shahabuddin and Whitehead's David Schneider produced their mosquito surrogate by injecting Plasmodium gallinaceum, which causes malaria in chickens, into the body cavities of fruit flies. The parasites matured through their normal life stages, producing infectious forms identical to those isolated from mosquitoes. Chickens infected with the fly-grown P. gallinaceum developed malaria and transferred the parasites to susceptible mosquitoes when the insects fed. These studies proved that Drosophila could serve as an effective model organism for growing Plasmodium.

The researchers used the fruit fly model to discover the way most mosquitoes resist malaria infection. In the fly, immune cells called macrophages engulf and destroy the parasites at an early stage, before they can develop further, suggesting the usefulness of the fruit fly in identifying anti-parasite processes of malaria's natural carrier.

Shahabuddin notes that the new model allows them to study Plasmodium-insect interactions with a new set of genetic and biochemical tools long used with the fruit fly. "These studies will let us identify factors in the insect that are critical to Plasmodium survival, and may ultimately lead to improved ways of breaking the parasite's life cycle and blocking its transmission."

For more information: Mohammed Shahabuddin, Investigator, Laboratory of Parasitic Diseases, NIAID, Room 126, Building 4, 4 Center Drive MSC 0425, Bethesda, MD 20892-0425. Tel: 301-496-9389. Fax: 301-402-8536. Email: mshahabudd@niaid.nih.gov.