Publicador de contenidos

PlasmoSugars

Exploration of the singularities of the sugar nucleotide metabolism and description of novel glycosylation pathways in the malaria parasite

Foto: Sanz S et al, Sci Rep, 2016
Duración
01/01/2014 - 30/06/2017
Coordinador
Luis Izquierdo
Financiadores
MINECO (Spanish Ministry of Economy)

Glycosylation represents one of the most common and heterogeneous post-translational modifications of proteins, and complex glycoconjugates are involved in almost every biological process. Thus glycoconjugates play a major role in nearly every human disease.

Sugar nucleotides are the activated forms of sugars used as donor substrates in glycosylation reactions and our lab has precisely delineated the sugar nucleotide biosynthetic pathways in the malaria parasite. In contrast to the prevailing idea that the Plasmodium glycoconjugate structures are limited to glycosylphosphatidylinosytil (GPI) anchors, our works show that other sugar nucleotide and glycosylation pathways are active in the blood stages of the malaria parasite.

We aim to probe essential and/or unanticipated enzymatic steps in these metabolic routes that are unidentified in the P. falciparum genome. Among these unresolved issues are: i) the identity of the P. falciparum putative glucosaminephosphate N-acetyltransferase (GNA) that converts glucosamine-6-P (GlcN6P) to GlcNAc6P; ii) the source (and biological significance) of the UDP-galactose (UDP-Gal) pool detected in the blood-stages of the parasite. Furthermore, our previous studies have shown the presence of GDP-fucose (GDP-Fuc) pools through the asexual stages of P. falciparum life-cycle at levels comparable to other protozoan parasites. This, together with the incorporation of tritium labelled GDP-Fuc by cell extracts of the parasite, strongly suggests the presence of active fucosylation mechanisms in P. falciparum. Our works show that P. falciparum blood-stage cell lines with engineered alterations in the GDP-Fuc biosynthetic pathway are not labelled by the fucose-binding Ulex europaeus agglutinin I (UEA-I). Therefore, a fucosyl transferase could be involved in the synthesis of an uncharacterized UEA-I-glycotope on the surface of the parasite.

Detailed biochemical and genetic studies of these essential but much neglected biosynthetic pathways may improve our understanding of the parasite’s biology and provide urgently needed targets for chemotherapeutic intervention.

Total funding:

139,150 €

Nuestro equipo

PI

ISGlobal team

Otros proyectos

Ver proyectos pasados

MESA

La Alianza Científica para la Erradicación de la Malaria (MESA) tiene como objetivo avanzar en la ciencia de la erradicación de la malaria.

NHEPACHA

Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas

Estudio inmunológico de la vacuna RTS,S

Estudio de correlatos de protección frente a la malaria después de la vacunación con RTS,S/AS01E: Una evaluación inmunológica exhaustiva en el ensayo clínico de Fase III, doble ciego, aleatorizado, multicéntrico con un grupo control

Euroleish.net

Control of Leishmaniasis. From bench to bedside and community

GREPIMER

Grup de recerca en patología importada i malaties emergents i re-emergents

TESEO

Nuevos regímenes de quimioterapia y biomarcadores para la enfermedad de Chagas

ASINTMAL

Unravelling Disease Tolerance and Host Resistance in Afebrile 'P. falciparum' Infections: a Prospective Study in Mozambican Adults

ADAM

Administración masiva y focal de fármacos antimaláricos para avanzar hacia la eliminación de la malaria en Mozambique: acelerando la implementación de programas y políticas

MULTIPLY

MULTIple doses of IPTi Proposal: a Lifesaving high Yield intervention

Science4Pandemics

Citizens engagement digital platform for collective intelligence in pandemics

HIDDENVIVAX

Novel organ-on-a-chip technology to study extracellular vesicles-mediated cryptic infections in Plasmodium vivax malaria

MENA Migrant Health

Transforming data collection and surveillance to drive migrant health research, care and policy

SexMal

Social affairs and sex in P. falciparum: implications for malaria elimination

EpiGen

Building Scalable Pathogen Genomic Epidemiology in Ethiopia

SMART

Identifying Severe Malaria with a new Aptamer-based Rapid diagnostic Test

MalTransc

Transcriptional regulation of adaptation and developmental decisions in malaria parasites: from epigenetic variation to directed transcriptional responses

GenMoz

P. falciparum genomic intelligence in Mozambique

BOHEMIA

Broad One Health Endectocide-based Malaria Intervention in Africa