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Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomes

AuthorsLópez-Martín, C.; Pérez-Victoria, J. M. ; Carvalho, L.; Castanys, Santiago; Gamarro, Francisco
Issue Date2008
PublisherAmerican Society for Microbiology
CitationAntimicrobial Agents and Chemotherapy 52: 4030- 4036 (2008)
AbstractSitamaquine (WR6026), an 8-aminoquinoline derivative, is a new antileishmanial oral drug. As a lipophilic weak base, it rapidly accumulates in acidic compartments, represented mainly by acidocalcisomes. In this work, we show that the antileishmanial action of sitamaquine is unrelated to its level of accumulation in these acidic vesicles. We have observed significant differences in sitamaquine sensitivity and accumulation between Leishmania species and strains, and interestingly, there is no correlation between them. However, there is a relationship between the levels of accumulation of sitamaquine and acidotropic probes, acidocalcisomes size, and polyphosphate levels. The Leishmania major AP3δ-null mutant line, in which acidocalcisomes are devoid of their usual polyphosphate and proton content, is unable to accumulate sitamaquine; however, both the parental strain and the AP3δ-null mutants showed similar sensitivities to sitamaquine. Our findings provide clear evidence that the antileishmanial action of sitamaquine is unrelated to its accumulation in acidocalcisomes. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Identifiersdoi: 10.1128/AAC.00964-08
issn: 0066-4804
Appears in Collections:(IPBLN) Artículos
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