Leishmania genome reveals how this parasite that affects 12 million people adapt to environmental changes

Leishmaniasis is an important human and veterinary disease caused by the Leishmania parasite that affects 12 million people in more than 98 countries. Currently the disease is surfacing in Europe due to climate change and massive population displacement. It is known that the parasite adapts quickly to new environments, which has important consequences for the number of people affected with this disease. Therefore, the EU and recognized as an emerging threat to public health.

In an article published in the journal Nature Ecology & Evolution, scientists at the Institut Pasteur in Paris and the Center for Genomic Regulation (CRG) in Barcelona, ​​in collaboration with researchers at the Institute of Tropical Antwerp (ITM) Medicine and the University of Montpellier they have shown that the adaptation of Leishmania due to a frequent chromosome amplification, ie the incorporation of a greater number of chromosomes should. These variations in the number of chromosomes, called aneuploidy, are similar to those found in various cancers.

Este descubrimiento representa un importante paso hacia una mejor comprensión de la infección de Leishmania en humanos y, en concreto, en la resistencia de los parásitos a tratamiento, su patogenicidad, y su movilidad en diferentes tejidos. El nuevo avance, que pone de manifiesto la inestabilidad genómica de Leishmania, podría allanar el camino hacia la identificación de los mecanismos que facilitan la resistencia a tratamientos y contribuir a descubrir nuevos biomarcadores para mejorar el diagnóstico y el pronóstico de los pacientes.

Leishmaniasis is one of the five most important infectious diseases worldwide, with an estimated 350 million people at risk of infection. The disease causes a wide spectrum of clinical manifestations in its three forms (cutaneous, visceral and mucocutaneous) as a result of infection by the parasite Leishmania species. These unicellular parasites adapt to a large number of guests. As extracellular parasites grow inside the arenera fly which transmits Leishmania to various vertebrates, such as, for example, rodents, dogs, and humans. Once in the host, Leishmania grows within cells of the immune system, mainly macrophages, causing various pathologies that can lead to death of the host.

Leishmaniasis is one of the most neglected diseases and attract less attention. There is still no vaccine for humans and there are only a few treatments, all with significant restrictions regarding administration, toxicity or cost. For more difficulty, one of the main biological characteristics of Leishmania is its ability to accommodate a large number of unpredictable fluctuations in their host and difficult, and treatment. For example, generating resistance to new treatments easily.

To identify the genetic mechanisms that allow genomics adaptation of Leishmania, scientists at the Pasteur Institute in Paris and the Center for Genomic Regulation (CRG) in Barcelona, ​​in collaboration with researchers at the Institute of Tropical Antwerp (ITM) Medicine and the University of Montpellier have developed new techniques for comparative genomics based on the latest sequencing techniques and in-sillico analysis. Their work, published in the journal Nature Ecology and Evolution, shows for the first time the existence of a relationship between changes in the number of copies of a chromosome and selection of new alleles important for the survival of Leishmania.

The most surprising aspect of this work is the observation that manages to combine the selection Leishmania allele and maintaining a high genetic diversity. Typically, these two processes should be mutually exclusive and would expect a parasite under strong selection lose their genetic diversity. In contrast, Leishmania, frequent duplications of chromosomes can combine both processes. Thus the parasite retains its diversity by allowing a same combination of alleles is selected simultaneously in genetically diverse individuals.

Gerald Späth, Director of the Unit of Molecular Parasitology at the Institut Pasteur in Paris, who has led the experimental part of the study, comments: "Almost all basic research, applied, and clinical of Leishmania is done with parasites crop long term. Our study shows that the parasite genome evolves very fast. it is important to keep that in mind to study the biology of the parasite and find new biomarkers, treatment or vaccine candidates. the future of research in Leishmania should be made more inclusive way consider the genetic interactions between parasite, the vertebrate host and the insect vector, under clinically relevant conditions, eg using parasites short term culture and applying direct sequencing of tissues ".

Cedric Notredame, group leader at the Center for Genomic Regulation (CRG) in Barcelona, ​​who led the comparative genomics of this study, explains: "There has always been the belief that gene amplification is a way for adaptation, but now, our work shows that Leishmania, evolution has used this mechanism to the point of making it an essential step in the life cycle of the parasite. An important part of the work shows that other variations complex aneuploid,play an important role in some cancers role and we believe that the large accumulation of genomic data available to us now combined with in-sillico innovative techniques - like the ones we used for this study - soon allow us to have a better understanding of the relationship between aneuploidy and selection of alleles ".

Professor Jean-Claude Dujardin Institute of Tropical Medicine (ITM) in Antwerp says. "It took over five years to compile a set of genomic data unprecedented clinical samples in the Indian subcontinent and publish an initial analysis last year A great feature of modern science is that all genomic data need to be made public, enabling new partnerships, such as that resulting in this work we present here. it has also allowed us to establish a new partnership between ITM, the Institut Pasteur and CRG to fight against infectious diseases. "

The results of this original study are highly relevant to other human diseases dependent genomic instability, such as fungal infections or cancer, and open new avenues to discover treatments for leishmania based on the host and metabolic dependence of the parasite to prevent adaptive evolution of resistance to treatments for parasites. (Source: CRG)