Sydney
THE discovery of the protein that makes malaria a potential killer has
raised hopes for a new way of treating or preventing the disease. 杏吧原创s in
Melbourne, Australia, have discovered how the parasite that causes cerebral
malaria makes red blood cells stick to and clog capillaries in the brain. They
have also managed to stop cells sticking to mock human capillaries.
Plasmodium falciparum infects between 200 and 300 million people
each year and of these 2 to 3 million die. The parasite invades red blood cells
and produces proteins that form 鈥渒nobs鈥� on the cell surfaces. Some researchers
have suggested that it is these knobs that make the blood cells stick to
capillaries.
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A team from the Walter and Eliza Hall Institute of Medical Research (WEHI),
Monash University and the University of Melbourne decided to test this. They
suspected that a protein called KAHRP (knob-associated and histidine-rich
protein), which the parasite produces and which forms under the surface of the
knobs, is essential for knob production.
To confirm this, the team used a technique called 鈥済ene knockout鈥� to disrupt
the gene that codes for KAHRP in parasitised blood cells. By adding an extra
stretch of DNA to the gene, they blocked the production of the protein. Scanning
electron microscopy later showed that knobs no longer formed on the cells.
To check whether it is the knobs that cause the blood cells to stick to
capillary walls, the team mimicked the environment inside human capillaries
using a slide covered with the capillary wall receptors that attach to
parasitised blood cells. They passed unmodified parasitised cells with knobs and
knobless 鈥淜AHRP-knockout鈥� cells across the slide. The researchers report in
Cell (vol 89, p 287) that while the cells with knobs stuck, the cells
without knobs flowed easily over the slide.
鈥淧eople haven鈥檛 tried to do this before鈥攊t is a new approach,鈥� says
Katherine Trendholme of the Menzies School of Health Research in Darwin, a
centre for communicable diseases research. 鈥淭his work is very important and
颈苍迟别谤别蝉迟颈苍驳.鈥�
The researchers now plan to find out which parts of KAHRP are involved in
knob formation. 鈥淓ventually, this could lead on to the possibility of making
drugs that will block the function of KAHRP, and therefore block the formation
of knobs,鈥� says Alan Cowman of the WEHI, one of the team. However, he warns that
it may be some time before treatments appear: 鈥淲e鈥檙e taking short
steps鈥攚e鈥檝e still got a fair way to go.鈥�