Could this be malaria's Achilles heel?

November 06, 2017

Portuguese researchers at Instituto de Medicina Molecular (iMM) Lisboa have identified a defence mechanism by which the malaria parasite can survive inside its host's liver cells, a crucial stage where the parasite acquires the capacity to infect red blood cells causing the symptoms associated with this disease.

The Plasmodium parasite, responsible for malaria infection, replicates inside it's host's liver cells involved by a membrane that protects it against threats present in the intracellular environment, namely autophagy, a process that is triggered upon infection and in which cells degrade materials that are no longer necessary. Importantly, this process is dependent on a protein named LC3.

Although autophagy is activated by host cells after infection the malaria parasite is resistant to this cellular defence mechanism, unlike other more susceptible pathogenic agents. However, researchers led by Maria Mota have now found the Achilles heel of the malaria parasite: a protein named UIS3 which binds to LC3 and forms a type of protective shield against autophagy. Without this protection the parasite becomes vulnerable and is rapidly eliminated by the host.

The study now published in Nature Microbiology has revealed that parasites lacking the UIS3 protein cannot survive inside mice liver cells. However, if the host's autophagy capacity is compromised the parasite gains back its capacity to infect cells.

These results show that UIS3 protein could become a possible target for the development of novel targets against the malaria parasite, namely against the hepatics forms of this disease which, in some Plasmodium species, may persist in a dormente state and cause symptoms several years after the time of first infection.

It is particularly relevant to identify new therapeutic targets at a time where several cases of drug resistance begin to occur, specifically in Southeast Asia. In the future, the team wishes to identify compounds that can block the parasite's capacity to inhibit cellular autophagy and test its efficiency as novel drugs against malaria.

iMM Lisboa

The Instituto de Medicina Molecular in Lisbon (Portugal) is a private non-profit research institute that offers a vibrant scientific environment where world-class ingenious scientists with an ambitious research portfolio are supported by state-of-the-art technology, aiming to maximize creativity towards discoveries without boundaries. In spite of iMM's young age (created in 2002), several iMM findings, spanning from basic to translational research, are already being applied to improve human health.

Instituto de Medicina Molecular

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to