- Two enzymes and a molecule that
can prevent the survival of the malarial parasite has been identified.
- These enzymes block the
transmission of the parasite from mosquitoes to humans and vice versa.
- The discovery could lead to the
development of new drugs for malaria.
identified enzymes which are essential for the survival
of the malarial parasite can help inhibit the survival of the parasite.
the two proteases and a molecule that inhibit the survival of the parasite, a
research team at the Universities of Geneva (UNIGE), Switzerland, and Bern
(UNIBE) have brought a new hope in the fight against malaria.
‘Two proteases essential for the survival of Plasmodium and transmission of the infection could be possible drug targets for malaria.’
could lead to the development of new drugs which can block the parasite
development in humans, as well as the transmission from
mosquito to humans.
parasitic disease that is transmitted from an infected female Anopheles mosquito
to humans. There are 5 species of the malarial parasite Plasmodium which infect
- Plasmodium falciparum
- Plasmodium malariae
- Plasmodium knowlesi
- Plasmodium ovale
Of these five,
Plasmodium falciparum is the most deadly parasite that kills more than 500,000
people per year. About 80% of those who die of malaria are children under the
age of five.
Methods for Malaria
classifies malaria as uncomplicated which results in symptoms, but clinical
tests do not indicate any vital organ dysfunction and complicated malaria which
can cause organ failure.
can lead to anemia (low levels of hemoglobin), cerebral malaria resulting in
abnormal behavior, acute respiratory distress syndrome
hyperparasitemia, low blood pressure, acute kidney failure, and hemoglobinuria.
The drugs given
to treat malaria sometimes fail due to:
- Disease resistance
- Limited action of the drug which fails
to block the transmission of the infection and allows the parasite to
proliferate in the blood.
endemic in 91 countries according to the WHO. Most malaria cases and deaths
occur in sub-Saharan
Africa, however, South-East Asia, Latin America and the
Middle East regions are also at risk.
individuals living in endemic areas develop natural immunity against malaria,
when bitten again by a mosquito, they can transmit the parasite allowing the
disease to spread further.
Therefore, it is necessary to develop molecules that target the forms of the
parasite by which it infects the liver and also the forms of the parasite that
infect the blood.
that Trap the Parasite
A team of
researchers led by Professor Dominique Soldati-Favre, a microbiologist at UNIGE
Faculty of Medicine, discovered new targets for intervention.
The survival of
Plasmodium and its ability to spread the infection crucially depends on the way
it enters and exits the host cells. By taking a closer look at the step
critical for the parasite invasion, two enzymes which generate infection from
the host cells have been identified.
has a very complex life cycle and encounters different host cells, whether in
the blood, liver or even in the mosquito gut. Strikingly, it uses the same two
aspartic proteases at each of these steps", states Volker Heussler,
professor at the Institute of Cell Biology at the University of Bern and
co-author of the study.
enzymes that act as molecular scissors and cleave proteins to control their
- One of the newly identified protease
is essential for the maturation of factors involved in penetrating through the
plasma membrane of infected cells.
- The second acts on adhesins which are
cell-surface components that facilitate adhesion to the host they are
infecting. These two proteases are therefore key elements for the survival and
spread of Plasmodium.
Proteases - a Powerful Inhibitor of the Parasite
uncover a crucial step in preventing the infection of Plasmodium from the
mosquitoes to humans. Aspartyl proteases are now proved to be effective in
preventing parasite infection.
re-examined these inhibitors in the light of our discovery," reports
Mathieu Brochet, professor at UNIGE Faculty of Medicine, "and one of them
proved to be particularly effective in blocking the two proteases we
Dominique Soldati-Favre explains that, since this inhibitor blocks two enzymes
rather than just one, the probability that both will develop resistance at the
same time is extremely low.
belongs to the taxonomy of Apicomplexa which are a group of parasites that
infect a wide spectrum of hosts that includes pathogens for both humans and
animals. The discovery could therefore help in parasite control to other
diseases that involve Plasmodium.
- Malaria - Key Facts - (http://www.who.int/mediacentre/factsheets/fs094/en/)
- Beatrice Autino, Alice Noris, Rosario Russo and Francesco Castelli. Epidemiology of Malaria in Endemic Areas, Mediterr J Hematol Infect Dis. (2012), doi: 10.4084/MJHID.2012.060. Dominique Soldati-Favre, Volker Heussler. A new weapon against malaria, Science (2017).