Microbial collectivism: a breakthrough in Leishmaniasis research

In a previous study, molecular parasitologists from ITM sequenced the genome of different Leishmania strains isolated from different patients with leishmaniasis. This involved bulk sequencing of the millions of cells that made up each strain and showed that the cell populations differed in the average number of different chromosomes. In humans, chromosomes must always occur in pairs. Variations in the number of copies are associated with diseases such as cancer or disabilities such as Down's Syndrome. For the parasite, this ability to change the chromosome copy number gives it an advantage.

A survival kit for drugs and vaccines

In their new study -funded by the Flemish Department of Economy, Science and Innovation- the ITM scientists went a step further. Gabriel Negreira, a Brazilian PhD student and first author of the study, says: “Using a revolutionary DNA technology, called single cell genome sequencing, we were able to 'sequence' each cell separately within one patient's population of cells.” The authors found that within one cell population, these cells also differed individually. This phenomenon is called mosaic aneuploidy. "The obvious question is why mosaic aneuploidy occurs so quickly in parasites derived from a single individual cell," adds Dr Malgorzata Anna Domagalska, leader of this research project. "We think that each of these cells contains a survival kit for a certain environmental stress. If a certain stress occurs, for example exposure to a drug, the entire population of cells may disappear, except for the one cell that contains the right survival kit, which could then restore the population. Population over individuals, a kind of microbial collectivism." Mosaic aneuploidy shows how versatile parasites can be and how they can escape drugs and vaccines. “We, scientists, need to be creative and undertake a next step in the arms race against these ‘clever’ parasites. Among others, we hope in the future to understand the mechanisms of mosaicism and block it. This could provide new avenues for drugs," explains Prof Jean-Claude Dujardin, head of the Molecular Parasitology unit at ITM.

Neglected diseases are high on ITM’s agenda

Leishmaniasis is an infectious disease caused by a parasite and transmitted by the bite of a sandfly. The consequences can be fatal or stigmatising. It affects 300,000 people each year, in no less than 88 countries including southern Europe. This makes Leishmaniasis one of the most important parasitic diseases after Malaria. To this day, there is no vaccine and only a limited number of drugs. Leishmaniasis belongs to the 'neglected diseases', a group of 20 infectious diseases including, among others, sleeping sickness and rabies, which occur mainly in the developing world and affect especially those living in poverty and poor hygienic conditions. At ITM, neglected diseases are high on the agenda. ITM conducts clinical, epidemiological and biomedical research activities to fight these diseases.

Link

• https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkab1203/6459083