Malaria: Mutant Parade

15. September 2010
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Many resistances, modestly effective vaccinations: The fight against malaria stagnates. Now US researchers want to attack the problem with a completely different approach: They created a mutated Anopheles, a mosquito that doesn’t care at all about malaria plasmodia.

Pathogens depending on humans as carrier can be eradicated by consistent vaccination programs. That’s a known fact. But with malaria the situation is not that simple: The Anopheles mosquito is a grateful host for plasmodia responsible for malaria and they enjoy infecting it in great numbers. As long as this mosquito is on the rampage, the danger of a malaria infection exists.

The bible of mosquitoes. The book of Genesis.

Reversed it remains true as well: In places where malaria had been eradicated successfully, like in Southern Europe, it worked only with a reroute via measures against the mosquito respectively by draining swamps. On the other hand this approach clearly meets its limits in the tropics. So there mainly vaccinations as the weapon against malaria are discussed and tested in clinical studies – in addition to the highly effective mosquito nets. Similar to the AIDS-virus, the malaria plasmodium is not exactly predestined to vanish with a simple vaccination. This one vaccination many hopes are currently built on does only work partially. Michael Riele, biologist and professor for entomology at the College of Agriculture of the University of Arizona/USA, is not convinced that it’s possible to get a grip on the malaria problem with that: “If the distribution of the malaria parasites is supposed to be stopped effectively, we need mosquitoes 100 percent resistant against it.” So he and his team have chosen another approach. They constructed a piece of genetic information and injected it into mosquito eggs, i. e. into eggs of the Anopheles stephensi, an important malaria carrier on the Indian subcontinent. The genetic construct actually was built into the mosquito genome after injection and passed on to future generations. In other words: The US researchers created an Anopheles mutant capable of passing on their mutation.

Mutated mosquito doesn’t want to be bothered with parasites

What kind of mutation is it exactly? The scientists target on one of several signal ways in the Anopheles mosquito. The implanted gene function like some kind of switch which permanently activates a certain signal protein named “Akt”. “Akt” is a transmitter that – among others – influences the growth of the larvae, the immune reactions and also the life span of the Anopheles mosquito. After successful genetic manipulation, the researchers fed the “Akt”-mutants with blood infected with malaria plasmodia to find out what the Anopheles mosquito would do with it. The result was something they did not expect: “We had hoped to see a certain effect on the growth rate of the mosquitoes, also regarding their life span and their sensitive to the parasites. But what we saw then was that our construct has completely blocked the infection”, says Riele who reported about this work in the magazine PLOS Pathogens.

Wanted: The advantage in the fight about the mosquito existence

The question of course is whom does a malaria resistant mosquito help if Anopheles mosquitoes fly all over the world more than ready to take on malaria plasmodia from human blood and transmit them with their next bite. Riele’s idea is to use mutants like his stephensi-mutant to supplant the Anopheles mosquito living naturally in an economic system. That would make it a Darwinian approach where an ecological niche until now filled with other, problematic mosquitoes would be replaced with an although related but not problematic regarding malaria mosquito species. The ideal case: This would turn off the tap for the plasmodia transmitting mosquitoes.

But it won’t be quite that simple. On one hand it will be hard to assess in the individual case what harm a mutant actually might do if being let loose in the wild. On the other hand, it requires yet another mechanism to provide the modified mosquitoes with a real survival advantage compared to their long-established brethren. Then – and only then – the infectious Anopheles species can be eradicated slowly in due time. But the scientists have not dealt with this question yet. The current mosquito would even have a disadvantage in the fight for existence “outside” since its life span is shorter as a consequence of the “Akt” mutation. But this doesn’t necessarily have to stay like that. Perhaps it’s possible to “fix” the issue with the life span by making another couple of mutations…

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