Unveiling the tactics of a parasite

The single-celled malaria-causing parasite Plasmodium, labelled with blue and green fluorescent dyes. Image credit: Peter Preiser.

Transmitted by Anopheles mosquitoes, malaria is a serious disease that has afflicted humans for thousands of years, as ancient artefacts and writings that describe symptoms of the infection such as high fevers and chills can testify. To this day, malaria remains a severe public health burden in tropical regions of Asia, Africa, and South America. In 2018, according to the World Health Organisation, there were an estimated 228 million cases of malaria worldwide and the disease claimed nearly half a million lives.

The widespread use of antimalarial drugs in recent years has led to the malaria parasite Plasmodium becoming more resistant to these drugs, which is a major concern for those involved in the fight against the disease. Drug-resistant malaria parasites, such as those resistant to artemisinin—an antimalarial compound often used in combination with other drugs —are especially prevalent in Southeast Asia.

Researchers believe that the development of Plasmodium’s resistance to artemisinin stems from improvements in its ability to repair its DNA after the drug has damaged it.

A team led by NTU’s Associate Vice President (Biomedical and Life Sciences)  Prof Peter Preiser, set out to investigate whether changes in Plasmodium’s DNA repair capabilities are a factor in emerging artemisinin-resistance in Southeast Asia.

The team, comprising researchers from Singapore, the US and Thailand, treated malaria parasites isolated from patients in Cambodia with artesunate—a drug derived from artemisinin. They measured how much damage the drug did to the DNA and found lower levels of DNA damage in resistant parasites compared to the non-resistant, or sensitive, parasites. The researchers then compared the genetic sequences of artesunate-resistant and -sensitive parasites and found that artesunate-resistant parasites carried mutations in several of their DNA repair genes, which might allow Plasmodium to repair drug-induced DNA damage more efficiently.

“Our study indicates that parasites with enhanced DNA repair may be able to tolerate more assaults on their DNA, thus contributing to the emergence of artemisinin resistance,” says Prof Preiser, who is from the  School of Biological Sciences at NTU.

“Understanding the factors that are important in the establishment and spread of artemisinin resistance in Southeast Asia is crucial for the development of new anti-malaria treatments,” the researchers say.

The study “K13-mediated reduced susceptibility to artemisinin in Plasmodium falciparum is overlaid on a trait of enhanced DNA damage repair” was published in Cell Reports (2020), DOI: 10.1016/j.celrep.2020.107996.