The single-celled parasite Plasmodium is the organism responsible for malaria. Unlike many pathogens that are passively transported by bodily fluids, Plasmodium is an active traveler. The parasite purposefully moves through its hosts, a capacity that is fundamental to every stage of its complex life cycle. Without this ability to self-propel, it could not complete the journey required to cause and transmit disease. This motility allows the parasite to seek out, penetrate, and colonize different tissues in both its human and mosquito hosts.
The Engine of Plasmodium Movement
The parasite’s primary method of locomotion is gliding motility, which allows it to move smoothly over surfaces without changing its cellular shape. This movement is powered by an internal molecular engine known as the glideosome, a complex of proteins located just beneath the parasite’s plasma membrane. The system generates forward propulsion without the use of external structures like cilia or flagella.
At the heart of this machinery is an actin-myosin motor. This motor, composed of actin filaments and a specialized protein called Myosin A, generates the physical force that drives the parasite. It is anchored to the parasite’s inner membrane complex, a stabilizing structure that gives the cell its shape and resilience.
This internal motor connects to external proteins called adhesins that act as its feet. These adhesins are pushed onto the parasite’s surface where they bind to substrates in the environment. Think of them as the sticky pads on a gecko’s foot or the treads on a tank, providing the necessary grip to pull the parasite’s body forward. Linker proteins form a bridge, connecting the motor on the inside to these substrate-gripping adhesins on the outside.
The entire system works through a coordinated cycle. The motor engages with actin filaments, pulling them toward the rear of the parasite. This action is transferred through the linker proteins to the adhesins. As the adhesins are pulled backward, the parasite’s cell body is propelled forward over the substrate, allowing it to glide steadily.
Navigating the Mosquito Host
The parasite’s journey begins inside a mosquito after it takes a blood meal from an infected person. Inside the mosquito’s gut, the parasite transforms into a motile form called an ookinete. This elongated, crescent-shaped cell must actively move through the dense, digesting blood meal to reach the midgut wall.
Once it reaches the gut wall, the ookinete must burrow through the peritrophic matrix, a protective layer lining the gut, and then invade one of the epithelial cells. It physically pushes its way through the tough cellular barrier to reach the other side. Without this migratory and invasive capacity, the parasite’s life cycle would hit a dead end within the mosquito’s stomach.
After crossing the midgut wall, the parasite develops into a stationary oocyst. Inside, it multiplies, eventually releasing thousands of new, highly motile parasites called sporozoites into the mosquito’s hemolymph. These needle-like sporozoites travel through this fluid, actively seeking out the mosquito’s salivary glands, which they must penetrate and colonize. This final step positions them for transmission during the mosquito’s next bite.
Invading the Human Host
When an infected mosquito bites a human, it injects sporozoites into the skin. These parasites activate their motility to navigate the dense tissue of the dermis. Moving at speeds of up to two micrometers per second, they search for a blood vessel to enter, a rapid movement that helps them evade patrolling immune cells and gain access to the circulatory system.
Once in the bloodstream, sporozoites are carried to the liver, where they prepare for the next invasion. To reach the liver cells, or hepatocytes, they must first cross the sinusoidal cell layer, a barrier of endothelial cells and resident macrophages. A sporozoite will often glide through several different hepatocytes before selecting one cell in which to settle and begin its replication phase. This entire process may take over an hour.
Inside the liver cell, the parasite multiplies into thousands of a new form, the merozoite. These merozoites are released back into the bloodstream to invade red blood cells. The invasion is remarkably fast, with a merozoite entering a red blood cell in less than a minute. This cyclical invasion and bursting of red blood cells is directly responsible for the classic symptoms of malaria, including fever and chills.
Targeting Motility for Disease Control
The parasite’s reliance on its movement machinery makes the glideosome an attractive focus for developing new antimalarial drugs. Since the glideosome is unique to Plasmodium, drugs designed to disrupt it would likely have minimal effect on human cells. Researchers are actively screening for compounds that can inhibit components of this motor, such as the Myosin A protein, to paralyze the parasite.
Another strategy involves developing drugs that lock the motor in place. Some compounds work by stabilizing the interactions between proteins in the glideosome, which prevents the dynamic changes needed for movement. This approach renders the parasite immobile and unable to complete its life cycle. Such drugs could be effective against multiple life stages, from the sporozoite traveling to the liver to the merozoite invading red blood cells.
Vaccine development also looks to this system for targets. The adhesin proteins—the “feet” that the parasite uses to attach to host cells—are prominent vaccine candidates. A vaccine that stimulates the human immune system to produce antibodies against these adhesins could physically block the parasite’s ability to latch onto cells. This would prevent invasion of the liver and red blood cells, though a challenge is the variability of these proteins.