Understanding how malaria parasites increase the resistance to medicines

Understanding how malaria parasites increase the resistance to medicines ...

Malaria parasites are vulnerable to certain medication therapies, but resistant to others, putting scientists at the forefront in theglobal fight against malaria.

The ANU team has characterisedtwomalariaproteins, known asPfMDR1 andPfCRT, who collaborate to transportdrugsaway fromareas where they exert their killingeffectandconcentratethem in "safe zones" that unfortunately rendered the treatmentsineffective.

Thefindingscould has led to further and longer-lasting treatment for malaria, a condition that claimed the lives of around 627 million people worldwide in 2020.

Anti-malarialtreatments are only effective at eradicating the disease, according to Dr Sarah Shafik of the ANU Research School of Biology. Alternative therapies are typically found outside of the stomach.

"We knew that parasitescan beresistanttosome medications are capable of treating toothers, but we didn''t know how it happened," said Dr Shafik, a co-author of the study.

"Our research shows thatPfMDR1 andPfCRT collaborate to alter the distribution of the drugswithin the parasite, allowing itto to escape the killing effects of one drug. In turn,thismeans that the parasite become more susceptible to another drug."

The discovery might leadscientiststodevelopnewtreatments orrepurpose existingdrugs to create new combinationtherapies that directly target thePfMDR1 andPfCRTproteinsandprevent the parasites from outsmarting the drugs.

Malaria parasites are constantly expandingand building resistance to currenttreatments, allowing them to escape death and stay one step ahead of scientists.

"This means thatmalaria therapy capable of treating patients today will not necessarily be effective in several years," Dr Shafik said.

"Theformergold standarddrug, chloroquine, which was used to treat malaria for 20 years has failed.Newtreatmentsthat are emerging only lasta fewyears before the parasitesstart to develop resistance to thesedrugs.

"This is because the parasite is really capable of muting certain proteins to avoid the harmful effects of the drugs."

The two proteins, according to scientists, are essential to the growth of parasites byrendering them intoactive using new and repurposed therapeutic therapies. They have a good chance ateradicatingmalaria.

"We are starting to gain a grasp of how to develop an effective treatment that doesn''t become obsolete over time by using a combination of anti-malarialdrugs that we already have in our repertoire, combined with other therapies that are used to treat HIV, for example." Dr Shafik said.

"Our intention is to sabotage PfMDR1 andPfCRT''s ability to control the movement ofdrugsinside the parasite, but also to inhibitthe essential natural function ofproteins, which helps the parasite grow."

According to Dr Shafik, the researchers''''discovery might help in the development of new types of cancer therapies.

"There is a protein fromhumancancer cells that is similar toPfMDR1.We have developed a method to evaluate these types of proteins," DrShafiksaid.

"We might be on the verge of developing more successfulcancertreatments by characterizingthe human version ofPfMDR1 and figuring outwhich chemotherapy drugsitcanpump out of cancer cells."

The research is publishedinPLOS Biology.

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