Drug-resistance gene found—again

Consider it a case of mistaken identity, but one with health implications for hundreds of millions of people. Three years ago, researchers announced they had found a gene that, when mutated, enables the parasite that causes the majority of the world’s malaria to shrug off the widely used drug chloroquine (SN: 11/29/97, p. 340: https://www.sciencenews.org/pages/sn_arc97/11_29_97/fob1.htm). It turns out they were wrong.

Thomas E. Wellems of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and his colleagues can cheerfully admit that fact, however, because they contend they have now captured the right gene.

Many of the drug-resistant parasites have mutations in the original gene identified. But the scientists grew suspicious when they were unable to make the parasite, Plasmodium falciparum, resistant to chloroquine by endowing it with mutant versions of the gene. The investigators then took a closer look at the region of the parasite’s DNA linked to chloroquine resistance and found another gene.

Several alterations within this gene appear to make the parasite impervious to chloroquine, Wellems’ group reports in the October Molecular Cell. This time, the researchers transformed chloroquine-sensitive parasites into resistant ones by introducing mutant versions of the newfound gene. Wellems’ team is now investigating the function of the gene, work that may lead to versions of chloroquine that the parasite can’t beat.