Anti-malaria genes give mosquitoes an edge

Transgenic mosquitoes resistant to malaria infection outcompete normal mosquitoes when feeding on infected blood

By | March 20, 2007

Researchers are one step closer to creating a viable malaria-resistant mosquito, according to a study in this week's Proceedings of the National Academy of Sciences. The authors found that, when feeding on malaria-infected blood, transgenic mosquitoes resistant to malaria infection experienced both higher fecundity and lower mortality than normal mosquitoes. If such a mosquito could be introduced into the wild, "you may end up with populations that are refractory to the transmission of the parasite," predicted Peter Atkinson of the University of California, Riverside, who was not involved in the study. Previous work has shown that mosquitoes infected with the malaria parasite are less fit than uninfected mosquitoes. This observation led to the hypothesis that transgenic malaria-resistant mosquitoes may outcompete wild-type mosquitoes, said study senior author Marcelo Jacobs-Lorena of Johns Hopkins Bloomberg School of Public Health. However, other studies have shown that transgenic mosquitoes may suffer a loss in fitness that balances out any gains from malaria resistance. "It was believed that just the presence of the transgene is a detriment," Jacobs-Lorena said. Led by Mauro T. Marrelli, also of Johns Hopkins, the researchers compared the fitness of wild-type Anopheles stephensi to that of mosquitoes expressing a peptide called SM1, which prevents the malaria parasite from invading the midgut. These transgenic mosquitoes cannot become infected with Plasmodium berghei, a malaria parasite that infects mice. The researchers placed equal numbers of wild-type and transgenic mosquitoes in a cage and fed them Plasmodium infected mouse blood. After nine generations, transgenic mosquitoes made up about 70% of the population. Additional experiments showed that transgenic mosquitoes had both higher fecundity and lower mortality than wild-type mosquitoes when fed blood containing reproducing parasites. "It's very nice work," Atkinson said. "Some people have always said that if we make these things transgenic, they'll just be so unfit because they're genetically altered that they'll never be of any use, [so] it's actually very encouraging news." Previous studies have shown that a different type of malaria-resistant mosquito cannot outcompete wild-type mosquitoes. However, those transgenic mosquitoes fought the malaria parasite by upregulating the immune response, which "may impose costs on the mosquito that equal, or even outweigh, the benefits of not being infected," according to Hilary Hurd of Keele University in Staffordshire, UK, who was an author on these previous studies but was not involved in the current work. "The advantage of the SM1 peptide is that it is not part of the natural immune system and appears to inhibit infection by blocking parasite invasion rather than killing the parasite," Hurd told The Scientist in an Email. In order to have a viable system that could be introduced into the wild, scientists will still need to come up with a genetic drive mechanism to encourage the transgene to spread among mosquito populations, Jacobs-Lorena said. Even though transgenic mosquitoes outcompete wild-types in the lab, this is probably not sufficient "to promote introduction of the gene into the wild by itself," he said. But their results suggest that "we may need not as strong a drive force as originally predicted in order to accomplish this goal." Another important step is to replicate the findings using human malaria parasites in their natural mosquito vectors, according to Robert Sinden of Imperial College London, who was not involved in the study. "If the results are repeated under these conditions we will have reason to be optimistic for the future." Melissa Lee Phillips Links within this article L. Pray, "Scientists want to create a new kind of mosquito," The Scientist, November 25, 2002. M. Marrelli et al., "Transgenic malaria-resistant mosquitoes have a fitness advantage when feeding on Plasmodium-infected blood," PNAS, March 27, 2007. ' H. Black, "Scientists refining methods for genetically altering insects," The Scientist, October 13, 1997. M. Goozner, "Beating malaria," The Scientist, December 1, 2006. Peter Atkinson H. Hurd, "Manipulation of medically important insect vectors by their parasites," Annual Review of Entomology, 2003. ' Marcelo Jacobs-Lorena F. Catteruccia et al., "Impact of genetic manipulation on the fitness of Anopheles stephensiaa mosquitoes," Science, February 21, 2003. J. Ito et al., "Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite," Nature, May 23, 2002. A.M. Ahmed, H. Hurd, "Immune stimulation and malaria infection impose reproductive costs in Anopheles gambiae via follicular apoptosis," Microbes and Infectiona, February 2006. Hilary Hurd Robert Sinden


March 21, 2007

Manipulation of mosquitoe genes to make resilient to malaria infection is very interesting but requires some thinking about its utility under field conditions. Moreover, we have read many such manipulations under the broad heading of "biological control". I wonder how many of such novel and laboratory conceived ideas have been successfully applied to field conditions? How far this research is going to be practically useful? Billions of dollars have been spent to control mosquitoes and good old "DDT" is back into action. Yet mosquitoes are resilient for control and they are still propagated without any impedence. No doubt vectors play very important role in dissemination of infection. This work, in my opinion should change its direction. They should consider the possibility of making the mosquitoes sterile by gene manipulation. If such approach can be achieved, then one can envisage the mosquitoe population undergoing sterility and thereby a direct hit on vector dissemination. This may have a broader applications and can be applied to many other vector-borne infections. Best of luck in their research.

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