Objetivo
Leishmaniasis has become the second most important human parasitic disease, affecting more than 12 million people worldwide. Its visceral form is always mortal in the absence of treatment. The disease is spreading since 1993, mainly due to the appearance o f resistance to the current drugs Glucantime and Pestontam. Thus, in some tropical hiperendemic areas, most cases are non-responsive to the treatment, whereas in Spain and other Mediterranean countries, drug-resistance leishmaniasis keeps on spreading as t he number of patients co-infected with HTV increases. Therefore, there is an urgent need for developing new drugs. Miltefosine is the most promising alternative, and it has become the first oral drug registered to treat visceral leishmaniasis.
As in the ca se of cancer cells resistant to the chemotherapy, ABC (ATP Binding Cassette) transporters over-expression is responsible of the appearance of parasites resistant to many of these drugs, including Glucantime, Pestontam and miltefosine. Only three classes of ABC transporters have been studied in Leishmania, but the number of members of this family increases continuously as the parasite genome project is being developed. The objective of this project is to study the functional role of some of these new ABC genes. We plan to analyse their implication in key biological functions of the parasite to check their potential as new drug targets for leishmanicidal agents. Moreover, we will determine the ability of these transporters to confer resistance to miltefosine and other drugs. With this aim, we will generate mutant parasites over-expressing or deleting these genes, and analyse the resulting phenotype.
Ámbito científico
- medical and health sciencesclinical medicinepsychiatrysleep disorders
- medical and health scienceshealth sciencesinfectious diseasesmalaria
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemultidrug resistance
- natural sciencesbiological sciencesgeneticsgenomes
Convocatoria de propuestas
FP6-2002-MOBILITY-11
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Régimen de financiación
ERG - Marie Curie actions-European Re-integration GrantsCoordinador
MADRID
España