Scientists have discovered the genetic secret behind the ability of the malaria parasite to evade attack by the human immune system.
They have shown how it can turn on and off genes that manufacture a series of 'cloaking' proteins used as camouflage.
If one protein is recognised by the immune system, the parasite simply produces another type.
The study, by Howard Hughes Medical Institute researchers based in Australia, is published in Nature.
"It's like a leopard being able to change its spots"
The parasite plasmodium falciparum is responsible for the deadliest form of malaria, claiming around one million lives worldwide each year, with another two million possibly linked to the disease.
It is highly skilled at sneaking past the body's immune defences with the help of a wardrobe of cloaking disguises.
The latest study shows how the parasite can turn on one cloaking gene, and keep dozens of others silent until each is needed in turn.
Key DNA
The key is a DNA sequence near the start of a cloaking gene, known as the gene's promoter.
This not only turns up production of its protein, but also keeps all other cloaking genes under wraps.
Malaria parasites enter human blood from infected mosquitoes.
They decorate the surface of the blood cells they occupy with a protein called PfEMP1.
But a small percentage of each generation of the parasite switches to a different version of this protein, which the immune system has never seen before, and so does not target for attack.
This enables a new wave of infection to take place before the immune system catches on, and launches a counter offensive.
Researcher Dr Alan Cowman, based at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, said: "It's like a leopard being able to change its spots.
"New forms come up, and the immune system beats them down again. Because of this a lot of people think you need five years of constant exposure to malaria in its different disguises to gain immunity."
The gene family responsible for the key protein comes in 60 different varieties, all very subtly different from each other.
The latest research shows that activation of a gene promoter is enough not only to trigger activity in one of these genes, but also to silence the 59 others.
The researchers now hope to identify the proteins that unpack and activate the promoter region.
Eventually, they hope their work may lead to new types of therapies that interfere with the parasite's immune evasion strategies.
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