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Antimalarial resistance to drug not passed on to future generations

April 14, 2016

Parasites that develop resistance to the antimalarial drug atovaquone cannot pass this resistance on to offspring, a new study suggests, because their lifecycles are often disrupted by the drug's mechanism. Atovaquone is a drug that has been used to treat malaria, a mosquito-borne disease caused by parasites. But, the parasites can develop resistance to this drug, and there is concern that this resistance will spread, as it has for other antimalarials. Mutations in the cytochrome b (cytB) gene are known to drive resistance. Therefore Christopher Goodman et al. studied three atovaquone-resistant strains of a malarial parasite that infects rodents, each strain containing a different mutation in their mitochondrial cytB gene. They found that two of the gene mutations resulted in developmental defects in the parasite zygotes, and the third mutation resulted in complete infertility in the parasites due to severely impaired female germ cells (reproductive cells). Cross breeding parasites with and without these mutations showed that the mutations are not passed on to offspring. From 44 separate transmission attempts involving 750 mosquito bites, atovaquone resistance transmission was only observed once, and this mutant was unable to transmit further despite seven attempts. The cytB gene is encoded in mitochondrial DNA, which plays an important role in mitochondrial electron transport processes upon which parasites are particularly reliant during the stage when they reside in mosquitos. It appears that atovaquone-resistant mutations severely impair the lifecycle of the parasites when they are living in mosquito hosts, and thus that these mutations cannot be passed on. In the human malaria parasite Plasmodium falciparum, the researchers identified similar mutations that impaired the ability of the parasites to infect mosquitos, as well as the number of oocysts produced when infection did occur.
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American Association for the Advancement of Science

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