James Dvorak has devoted his career to the study of malaria, `one of the major maladies of our time.' Over the years, Dvorak has probed the intricate details of the malaria parasite's voyage inside its mosquito host. Now, working with Mayumi Akaki, Dvorak has found that the sporozoite stage of the malaria parasite's lifecycle finds the chemical lure of mosquito salivary glands irresistible (p. 3211).
The malaria parasite divides its lifecycle between two hosts: humans and mosquitoes. When a mosquito gorges on a blood meal from a person infected with malaria, it unwittingly sucks the parasite's gametocytes into its body. Once inside the mosquito, the gametocytes fuse and the resulting ookinete invades the mosquito's gut wall. Eventually, the developing oocyte bursts, releasing delicate spindle-shaped sporozoites into the insect's circulatory system. Coursing around the mosquito's body, the sporozoites are incredibly selective; they only invade the insect's salivary glands, ready for the mosquito to feast on its next human victim.
Dvorak wanted to know how sporozoites make their way to a mosquito's salivary glands. `This is a tricky question to answer', he says, explaining that the salivary glands are tucked away in a mosquito's thorax, which is covered by an opaque cuticle that makes it impossible to study the glands directly under a microscope. Dvorak suspected that sporozoites use a chemical cue to locate the salivary glands as they are swept along by the mosquito's circulatory system. Teaming up with Akaki, he painstakingly developed an in vitro system to discover whether sporozoites are attracted to mosquito salivary glands.
First, Dvorak and Akaki needed to show that sporozoites can steer themselves in a particular direction. If you place the parasites on a glass slide and peer down a microscope, you'll see that the sporozoites glide around in elegant circles. `But that doesn't get us anywhere, and it certainly doesn't get the sporozoites anywhere!' Dvorak remarks. To find out whether the parasites were simply being constrained by the 2D environment, Dvorak and Akaki created 3D surroundings that would allow the parasites to show off their locomotor skills. They developed a tiny chamber that holds a microscopic amount of Matrigel, a semi-solid matrix, and loaded the chamber with green fluorescent protein-expressing sporozoites. Capturing every move of the fluorescent parasites using a video camera and a 3D motion-tracking program, they were delighted to see that the sporozoites adeptly travelled through the Matrigel using a corkscrew-like motion.
But are the sporozoites attracted to mosquito salivary glands? To find out, Dvorak and Akaki added salivary gland extract to one end of the chamber. Sure enough, the sporozoites navigated towards the extract. After carefully ruling out other explanations for the sporozoites' movements, the pair concluded that the parasites use chemotactic gradients to locate a mosquito's salivary glands.
Dvorak and Akaki's findings offer a tantalising new approach in the fight against malaria. Treating a mosquito with an anti-chemotactic substance to counteract the sporozoites' chemical attraction to the salivary glands could leave the parasites stranded without a map on their long journey through the mosquito body.
- © The Company of Biologists Limited 2005