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Arsenic-Containing Antibiotic Combats Malaria in Lab Models

Microscope image of a patient's blood smear indicating the presence of Plasmodium falciparum.
A thick film human blood smear, extracted from a patient with a malarial infection, revealing the presence of a Plasmodium falciparum gametocyte. Credit: CDC/ Dr. Mae Melvin
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A study has revealed an antibiotic called arsinothricin (AST) – the only known natural arsenic-containing antibiotic – may inhibit the proliferation of malaria-causing parasites in human cells and prevent their transmission to mosquitoes. The research is published in Microorganisms.

The need for new antimalarial drugs

Approximately 240 million malaria cases are reported every year across the globe. Most cases occur in Africa, which carries a disproportionately high share of the global malaria burden.

Now, malaria is becoming a growing concern in the United States. The U.S. Centers for Disease Control and Prevention (CDC) recently issued a health advisory about several malaria infections that were locally acquired in Florida and Texas, marking the first time it has spread in the U.S. since 2003.

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“Current antimalarials don’t completely stop transmission, meaning patients can continue to infect mosquitoes before they recover,” said Dr. Masafumi Yoshinaga, lead author of the study and associate professor of cellular biology and pharmacology at Florida International University (FIU). “Developing new potent multi-stage drugs is imperative to ensure malaria elimination and eradication.”

A team from FIU’s Herbert Wertheim College of Medicine developed AST to combat the rise of antibiotic-resistant bacteria, previously demonstrating its success in preventing the growth of resistant strains of E. coli and tuberculosis-causing Mycobacteria.

The fact that AST contains arsenic – a lethal poison – may send alarm bells ringing for some, but it is not pure arsenic. Arsenic-based medications were used in the early 20th century to treat syphilis until the development of penicillin, and some still have limited usage for treating “sleeping sickness” caused by the parasite Trypanosoma brucei. Now, new and novel arsenic-containing compounds have the potential to be used as antimicrobial agents.

In the current study, the team turned to AST to see if it might have similar success against malaria: “We found AST is a promising lead compound for developing a new class of potent multi-stage antimalarials,” said Yoshinaga.

Preventing transmission to mosquitoes

Malaria spreads when a mosquito bites someone with malaria, and the disease-causing parasites in the blood infect the mosquito. Ten days later, infected mosquitoes can bite another person and transmit the disease to them.

When FIU researchers tested AST on human liver, kidney and intestinal cells grown in the laboratory, they found that AST targeted the malaria-causing parasite Plasmodium falciparum within human cells after infection and left the human cells undamaged.

Unlike other antimalarial drugs, the researchers discovered that AST also prevented P. falciparum from infecting mosquitoes that go on to transmit the disease. Therefore, AST has the potential to prevent the parasites’ spread to mosquitoes and break the malaria life cycle.

The team has received a U.S. patent for the chemical synthesis and use of AST. Nonetheless, further research investigating how it enters human red blood cells is needed to understand how AST could become more effective against the parasite.

Additional research to generate effective antimalarials

Overall, this discovery paves the way for AST to one day be developed into an effective antimalarial drug for humans.

“What’s exciting about our research is it demonstrates how chemically different AST is from other drugs and that gets us even closer to drugs that are more effective,” said Professor Barry P. Rosen, one of the study’s authors and distinguished university professor at FIU. “We have a long way to go before we have a drug that goes to market, but this foundational work paves the way toward that goal.”

Reference: Yoshinaga M, Niu G, Yoshinaga-Sakurai K, et al. Arsinothricin inhibits Plasmodium falciparum proliferation in blood and blocks parasite transmission to mosquitoes. Microorganisms. 2023;11(5):1195. doi: 10.3390/microorganisms11051195

This article is a rework of a press release issued by Florida International University. Material has been edited for length and content.