A study led by Isglobal, a center imported by the «La Caixa» Foundation, has identified a Crucial weakness in Plasmodium falciparum, The parasite responsible for most malaria deaths. The findings, published in PLOS pathogensThey open the door to the development of new antimalar treatments that attack the parasite without being toxic to human cells.
Malaria is still one of the main causes of cooling and death in the world, specially in Sub -Saharia Africa. Given the increase in resistance, a real treatments, urgent resulting from new and more effective denim forms to combat the parasite.
«The challenge is that the parasites Plasmodium That cause malaria son eukaryotic organisms, such as us (that is, it shares many metabolic routes with our own cells), which makes it difficult to include drugs that are lethal for elalos but safe for humans, «he explains Luis IzquierdoIslobal researcher and senior author of the study.
In this work, Izquierdo and his team focused on a Metabolic route on which the parasite depends, known as the biosítosis of hexosamines. This metabolic route meets a function clove In the synthesis of essential molecules called glycosilfosphatidylinitol (GPI), which anchor crystical proteins on the surface of the parasite and help maintain its structure.
A metabolic step of the parasite
The team focused on a Enzyme called PFGNA1Essential for this and structural member Different from its equivalent in humans. The inactivation of the PFGNA1 gene in the parasite caused a drastic loss of these proteins and an incorrect location of the surface protein of the merozoíto 1 (MSP1), which defines a vital unpel in the invasion of the red blood cells. He Parasite development In the final stage of its cycle (schizon phase), it prevents its output of red blood cells and blocking the infectious.
“Our resulting confirms the central role of this metabolic route for the survival of the parasite and highlights this enzymatic step as a Critical vulnerability point«He says María Pía AlberioneFirst author of the study. «The great advantage,» adds left, «is that this enzyme is very different in humans: it has evolved independently in parasites such as P. falciparumwhich gives us the design opportunity drugs that attack the parasite without affecting human cells. ”
Previously investigations of the Left Group had already shown that the same metabolic route and enzyme are also based on Another parasite causes deferramence, Toxoplasma gondii. This strengthens the idea that pathogenic equis I share a «Achilles heel» common metabolica weakness that can be appointed to develop New and safer treatments.
Reference
Alberione MP, Avalos-Padilla and, Rangel Gw et al. The interruption of the biosynthesis of hexosamine harms the production of GPI and arrests the growth of plasmodium falciparum in Schizont Stages. Pathogens. DOI: 10.1371/Journal.Pat.1012832
