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Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains.


ABSTRACT: Understanding the mechanism(s) underpinning drug resistance could lead to novel treatments to reverse the increased tolerance of a pathogen. In this study, paromomycin (PMM) resistance (PMMr) was induced in three Nepalese clinical strains of Leishmania donovani with different inherent susceptibilities to antimony (Sb) drugs by stepwise exposure of promastigotes to PMM. Exposure to PMM resulted in the production of mixed populations of parasites, even though a single cloned population was used at the start of selection. PMM 50% inhibitory concentration (IC50) values for PMMr parasites varied between 104 and 481??M at the promastigote stage and 32 and 195??M at the intracellular amastigote stage. PMM resistance was associated with increased resistance to nitric oxide at the amastigote stage but not the promastigote stage (P?

SUBMITTER: Shaw CD 

PROVIDER: S-EPMC7187574 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Genomic and Metabolomic Polymorphism among Experimentally Selected Paromomycin-Resistant Leishmania donovani Strains.

Shaw C D CD   Imamura H H   Downing T T   Blackburn G G   Westrop G D GD   Cotton J A JA   Berriman M M   Sanders M M   Rijal S S   Coombs G H GH   Dujardin J C JC   Carter K C KC  

Antimicrobial agents and chemotherapy 20191220 1


Understanding the mechanism(s) underpinning drug resistance could lead to novel treatments to reverse the increased tolerance of a pathogen. In this study, paromomycin (PMM) resistance (PMM<sup>r</sup>) was induced in three Nepalese clinical strains of <i>Leishmania donovani</i> with different inherent susceptibilities to antimony (Sb) drugs by stepwise exposure of promastigotes to PMM. Exposure to PMM resulted in the production of mixed populations of parasites, even though a single cloned popu  ...[more]

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