| Autor: |
Schäfer, Carola, Tejera Nevado, Paloma, Zander, Dorothea, Clos, Joachim |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; February 2014, Vol. 58 Issue: 3 p1565-1574, 10p |
| Abstrakt: |
ABSTRACTAntimony-based drugs are still the mainstay of chemotherapy against Leishmaniainfections in many countries where the parasites are endemic. The efficacy of antimonials has been compromised by increasing numbers of resistant infections, the basis of which is not fully understood and likely involves multiple factors. By using a functional cloning strategy, we recently identified a novel antimony resistance marker, ARM58, from the parasite Leishmania braziliensisthat protects the parasites against antimony-based antileishmanial compounds. Here we show that the Leishmania infantumhomologue also confers resistance against antimony but not against other antileishmanial drugs and that its function depends critically on one of four conserved domains of unknown function. This critical domain requires at least two hydrophobic amino acids and is predicted to form a transmembrane structure. Overexpression of ARM58 in antimony-exposed parasites reduces the intracellular Sb accumulation by over 70%, indicating a role for ARM58 in Sb extrusion pathways, but without involvement of energy-dependent transporter proteins. |
| Databáze: |
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