PAROMOMYCIN RESISTANCE IN LEISHMANIA-TROPICA - LACK OF CORRELATION WITH MUTATION IN THE SMALL-SUBUNIT RIBOSOMAL-RNA GENE

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 mu g /ml of paromomycin were selected by exposing them to gradual increment s of this drug. Previous work in Escherichia coli, Tetrahymena, and ye ast mitochondrial mutants has demonstrated mutations in the E. coli sm all subunit ribosomal RNA at the 1409:1491 basepair position, or equiv alent positions in other organisms, resulting in basepair disruption. When the nucleotide sequence at both the DNA and RNA levels of the res istant L. tropica promastigotes cultured in the presence of paromomyci n was compared with those of the drug-sensitive parent, there was no s equence change at the putative mutation site. Paromomycin resistance i n L. tropica is apparently due to other mechanisms.