Paromomycin Resistance in Leishmania tropica: Lack of Correlation with Mutation in the Small Subunit Ribosomal RNA Gene

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  • Bureau of Biological Research and Department of Biological Sciences, Rutgers, The State University of New Jersey, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Piscataway, New Jersey
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The aminoglycoside antibiotic paromomycin is a potentially useful anti-leishmanial chemotherapeutic agent. Resistance to this antibiotic was studied using Leishmania tropica. Promastigotes resistant to 210 µg/ml of paromomycin were selected by exposing them to gradual increments of this drug. Previous work in Escherichia coli, Tetrahymena, and yeast mitochondrial mutants has demonstrated mutations in the E. coli small subunit ribosomal RNA at the 1409:1491 basepair position, or equivalent positions in other organisms, resulting in basepair disruption. When the nucleotide sequence at both the DNA and RNA levels of the resistant L. tropica promastigotes cultured in the presence of paromomycin was compared with those of the drug-sensitive parent, there was no sequence change at the putative mutation site. Paromomycin resistance in L. tropica is apparently due to other mechanisms.