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Antimicrobial Agents and Chemotherapy, December 2008, p. 4503-4506, Vol. 52, No. 12
0066-4804/08/$08.00+0     doi:10.1128/AAC.01075-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antimony Resistance and Trypanothione in Experimentally Selected and Clinical Strains of Leishmania panamensis

Centro Internacional de Entrenamiento e Investigaciones Medicas, Cali, Colombia

Received 16 April 2007/ Returned for modification 10 August 2008/ Accepted 14 September 2008

The participation of trypanothione in clinical and experimental antimony (Sb) resistance in Leishmania panamensis was examined by using specific inhibitors. Buthionine sulfoximine (BSO) significantly reversed the resistance to trivalent Sb (Sb^III) of promastigotes of experimentally derived Sb-resistant lines, supporting the participation of a trypanothione-mediated mechanism of resistance. In contrast, promastigotes of strains isolated at the time of clinical treatment failure and resistant to pentavalent Sb (Sb^V) as intracellular amastigotes were not cross resistant to Sb^III, and BSO had little or no effect on susceptibility. Difluoromethylornithine did not alter the Sb^III susceptibilities of experimentally selected lines or clinical strains. The mechanisms of acquired resistance emerging in clinical settings may differ from those selected by in vitro exposure to Sb.

Published ahead of print on 29 September 2008.

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