How the sleeping sickness protozoan evades capture
history provides examples of robbers who were masters at disguise. Charles Peace of 19th century England was
one. A scholarly gentleman during the day and a burglar by nightfall, he embarrassed even the Scotland Yard at its inability to apprehend him.
Science provided him with a rival.
The protozoan Trypanosoma brucei, which causes African sleeping sickness in humans is good at disguises. Transmitted by the
blood-sucking tsetse fly into a host's body, everytime the host's immune system comes close to apprehending it, the parasite changes the
appearance of its surface and makes its getaway. Working on the method involved in the escape, a team led by Catharine E Boothroyd from the
Rockefeller University, New York, observed that a double-stranded break (dsb) in the parasite's dna is crucial.
The parasite has a protective surface coat made of proteins attached to carbohydrates (glycoproteins). It is known as the variant surface
glycoprotein (vsg) coat. The glycoproteins are the surface antigens in reponse to which the immune system
releases antibodies. When the parasite modifies this coat by genetic manipulation, it changes its antigenic profile. This fools the host's immune
system. The genes responsible for the switching are called the vsg genes. At a time only one vsg gene is expressed while the others are silent.
Earlier studies have proved that a break in the double-stranded dna stimulates the switching but the exact
mechanism could not be demonstrated. The team was able to, for the first time, artificially induce such a break by introducing the enzyme
endonuclease into a specific region near the active gene.
The enzyme successfully induced the break and roughly half of all the cells in which a dsb was induced, modified
their coats, said the study reported in the April 15 issue of Nature. "The parasite clips off its dna close to
the vsg gene that is active. This confuses the replication machinery and to repair itself, it copies a new gene from
another chromosome," explained Boothroyd. Simply speaking, the dna inflicts self-damage to allow for a gene
switch which encodes for a variant surface coat. When the break was induced in some other part of the dna, it did
not cause switching. This proved how crucial the specific region near the active gene is.
"Creating free dna ends can pose problems to the dna replication machinery," said
Boothroyd. But it can also be useful, as it is to this parasite. "Some human immune cells break their dna at the
antigen receptor genes. The breaks are repaired in ways that help increase antibody diversity," added Boothroyd. In other words, this allows the
immune system to get better at fighting diseases.
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