Discovery of a potential therapeutic target to combat trypanosomes

October 26, 2017, CNRS

Yaser Hashem's team at the Laboratoire Architecture et Réactivité de l'ARN at CNRS's has discovered a new potential therapeutic target - located in the ribosome - to combat trypanosomes parasites. Using cryo-electron microscopy, researchers at the Institut de Biologie Moléculaire et Cellulaire (CNRS/Université de Strasbourg) have analyzed the structure of these parasites in details and revealed one of their potential weak points, which has remained undetected until now. This discovery opens the path to the development of new safer therapies that are less toxic and more specific against trypanosomes, the parasites causing the Chagas disease and the African sleeping sickness. This study is published on October 26, 2017 in Structure.

Trypanosomes, more generally called kinetoplastids, are unicellular responsible for numerous diseases of variable severity that can be lethal in the most severe cases. Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are probably the best known and cause the African sleeping sickness, Chagas disease and various Leishmaniasis, respectively.

Unlike bacteria, these organisms are eukaryotic that contain a nucleus, just like . The similarities, though low, between animal cells and trypanosome cells complicate some therapeutic approaches. For example, an antibiotic targeting given molecular machinery in trypanosomes such as the ribosome could harm human cells at the same time. Until now, researchers thought that eukaryotic ribosomes (molecules involved in protein synthesis) had extremely similar structures from one species of eukaryotes to another, such as for instance the case of humans and trypanosomes, making them almost untouchable. Recent technological advances made possible the visualization of the structure of the ribosomes from trypanosomes at near-atomic resolutions, thus small structural differences to the human ribosomes can now be seen and become a potential therapeutic target.

Yaser Hashem's team has particularly looked at the architecture of the Trypanosoma cruzi ribosome. Using - involving sample cryogenization, it allows biological structures to be visualized in their native state - in combination with mass spectrometry - using the mass of each element to determine a precise protein composition - they have brought to light a protein specific to the of trypanosomes: KSRP (kinetoplastid-specific ribosomal protein). In addition to being specific to these parasites, KSPR is essential to their survival since inhibiting its activity leads to death of the parasites. The exact role of KSRP in the protein synthesis remains unsolved.

This discovery of KSRP gives us a glimpse into possible future medical research for the development of new therapies against trypanosomes parasites. Elucidating the structure of this new protein could lead to designing molecules that can interact with and inhibit its activity in a highly specific way, without interfering with host cells. So the possibility of targeting and inhibiting KSRP in parasites will represent a safer alternative, and especially a more efficient alternative, compared to current treatments that are extremely difficult and toxic.

Explore further: News from the pathogen that causes sleeping sickness

More information: Jailson Brito Querido et al, The cryo-EM Structure of a Novel 40S Kinetoplastid-Specific Ribosomal Protein, Structure (2017). DOI: 10.1016/j.str.2017.09.014

Related Stories

News from the pathogen that causes sleeping sickness

June 22, 2017

The life-threatening African trypanosomiasis, also called sleeping sickness, is caused by protozoa of the species Trypanosoma brucei. A team at the Biocentre of the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, ...

New insights into the world of trypanosomes

August 23, 2017

Single specimens of the vermicular pathogens causing sleeping sickness swim inside the gut of the tsetse fly between blood cells which the fly has ingested from an infected mammal. This is where they start their week-long ...

Unusual protein production found in trypanosome mitochondria

August 30, 2017

Mitochondria, the power plants of the cell, have their own protein factories, although the cell apparatus could easily do the job for them. A special species of eukaryotes even has all the transfer-RNA it needs for protein ...

Recommended for you

Can China keep it's climate promises?

March 26, 2019

China can easily meet its Paris climate pledge to peak its greenhouse gas emissions by 2030, but sourcing 20 percent of its energy needs from renewables and nuclear power by that date may be considerably harder, researchers ...

What happened before the Big Bang?

March 26, 2019

A team of scientists has proposed a powerful new test for inflation, the theory that the universe dramatically expanded in size in a fleeting fraction of a second right after the Big Bang. Their goal is to give insight into ...

Cellular microRNA detection with miRacles

March 26, 2019

MicroRNAs (miRNAs) are short noncoding regulatory RNAs that can repress gene expression post-transcriptionally and are therefore increasingly used as biomarkers of disease. Detecting miRNAs can be arduous and expensive as ...

In the Tree of Life, youth has its advantages

March 26, 2019

It's a question that has captivated naturalists for centuries: Why have some groups of organisms enjoyed incredibly diversity—like fish, birds, insects—while others have contained only a few species—like humans.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.