Research News – 8

Anopheles (Mosquitoes) and their related cousins have a board meeting and the head of the scourge spurts out the following words:

near the Youth Hostel in Loch Ness , Scotland, 2009

I come from haunts of coot and hern
I make a sudden sally,
And sparkle out among the fern,
To bicker down a valley.
For men may come and men may go,
But we (I) go on for ever.

For men may come and men may go we will go for ever.

Full poem by Tennyson can be read here.

J. D. Keasling’s research group from California, Berkeley metabolically engineered Saccharomyces cerevisiae to produce artemisinic acid, a precursor for the antimalarial drug artemisinin. Ro et al write in their Nature paper in 2006:

Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.

After 7 years, Keasling’s group manage to engineer the organism further by incorporating a plant dehydrogenase and a second cytochome to produce artemisinin at a titer of 25 g per Litre. Their Nature paper (available for free) is aptly titled: High-level semi-synthetic production of the potent antimalarial artemisinin and conclude:

Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price.

Keasling’s video on eradicating malaria can be viewed here. The full length article on the discovery was published in ‘The New Yorker‘. Happy ending we thought but Nature has thought otherwise.

Scientists report that mosquitoes have developed resistance to insecticide used in the nets. The nets which were supposed to protect the humans, posed a selective pressure on the mosquitoes to evolve.(Like Gerri, in Inside No.9, a TV series produced by BBC, where a tramp takes control over his benefactor).

Gregory Lanzaro at the University of California, Davis, and his colleagues analysed DNA from more than 1,000 specimens of Anopheles coluzzii and Anopheles gambiae in Mali from 2002 to 2012. They found that a group of genes, including one for insecticide resistance, from A. gambia moved into A. coluzzii around 2006 when the two species mated.

Campaigns to encourage the use of insecticide-treated bed nets began in 2005 in this region, and the authors suggest that the nets favoured the selection of hybrid, insecticide-resistant mosquitoes.

Original article in the PNAS.

Dao et al conducted another kind of study where they researched the reason for the persistence of one particular species of Anopheles after a dry season.

Editor’s summary from Nature:

Malaria-carrying mosquitoes disappear in the dry season but appear suddenly when the rains come to sub-Saharan Africa. Their behaviour during the dry half of the year has long been something of a mystery. Here, Tovi Lehmann and colleagues report five-year surveys of mosquito densities throughout that reveal seasonal patterns in the population dynamics of three main vector species, and use these to infer dry-season behaviour. In two species (Anopheles arabiensis and A. gambiae s.s.) the dynamics are consistent with long-distance migration, and in the third (Anopheles coluzzii) with dry-season adult dormancy or aestivation. These natural history discoveries offer fundamental opportunities to improve malaria control, which remains a major public health challenge.

Dao et al; Nature

To combat a disease the quickness with which a drug decimates a population of a microorganism must be many orders of magnitude higher than the forces that shape the evolution of the microbe and its carrier. In the case of malaria the battle is not won yet as Anopheles is getting resistant to the insecticide and is clearly ahead of us.

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