BACKGROUND In view of the recent upsurge in the phenomenon of therapeutic failure, drug resistance in Leishmania, developed under natural field conditions, has become a great concern yet little understood. Accordingly, the study of determinants of antimony resistance is urgently warranted. Efflux transporters have been reported in Leishmania but their role in clinical resistance is still unknow...

Although oral miltefosine represented an important therapeutic advance in the treatment of leishmaniasis, the appearance of resistance remains a serious threat. LMDR1/LABCB4, a P-glycoprotein-like transporter included in the Leishmania ABC (ATP-binding cassette) family, was the first molecule shown to be involved in experimental miltefosine resistance. LMDR1 pumps drugs out of the parasite, the...

BACKGROUND Current treatments for cutaneous leishmaniasis are limited by their toxicity, high cost, and discomfort and the emergence of drug resistance. New approaches, including combination therapies, are urgently needed. We performed a double-blind, randomized trial of therapy with parenteral antimony plus topical imiquimod, an innate immune-response modulator, versus therapy with antimony al...

The generation of antimony clusters in the size range from Sb to SbSoo is reported. The clusters are created by inert gas condensation and detected by a time-ofiflight mass spectrometer. Condensation of clusters of knvwn sizes onto a cold substrate is suggested as a technique which enables investigations of amorphous substances as a function of order. To reveal the topology of amorphoussolids a...

Pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate, have been used for more than half a century in the therapy of the parasitic disease leishmaniasis. Even though antimonials are still the first-line drugs, they exhibit several limitations, including severe side effects, the need for daily parenteral administration and drug resistance. The molecular structure of ...

Plasmid-mediated resistance to arsenate, arsenite, and antimony(III) is coordinately induced by arsenate, arsenite, antimony(III), and bismuth(III). Resistance to arsenate was recently shown [Silver, S., Budd, K., Leahy, K.M., Shaw, W.V., Hammond, D., Novick, R.P., Willsky, G.R., Malamy, M.H. & Rosenberg, H. (1981) J. Bacteriol. 146, 983-996] to be due to decreased accumulation of arsenate by t...

Pentamidine (PEN) is a second-line agent in the treatment of leishmaniasis whose mode of action and resistance is not well understood. Here, we used a genetic strategy to search for loci able to mediate PEN resistance (PENr) when overexpressed in Leishmania major. A shuttle cosmid library containing genomic DNA inserts was transfected into wild-type promastigotes and screened for PEN-resistant ...

Leishmaniasis causes significant morbidity and mortality worldwide. The disease is endemic in developing countries of tropical regions, and in recent years economic globalization and increased travel have extended its reach to people in developed countries. In the absence of effective vaccines and vector-control measures, the main line of defence against the disease is chemotherapy. Organic pen...