Gene amplification in amphotericin B-resistant Leishmania tarentolae.
Two Leishmania tarentolae cells were selected step by step for resistance to the polyene antibiotic amphotericin B, a second-line drug against the parasite Leishmania. One of the mutants was cross-resistant to ketoconazole. DNA amplification was observed in both mutants. The amplicons were extrachromosomal circles and were derived from different chromosomes. In one mutant the circle was unusually stable as it remained within the cell despite numerous passages in the absence of the drug. A circumstantial link between the copy number of amplicons and the resistance levels was established. Gene transfection experiments indicated that the link between the locus amplified and the resistance levels was not straightforward and possibly several mutations act together to lead to amphotericin B resistance.
Singh
A K
AK
Département de Microbiologie, Centre de Recherche en Infectiologie du Centre de Recherche du CHUL, Faculté de Medicine, Université Laval, Ste-Foy, Québec, G1V 4G2, Canada.
Papadopoulou
B
B
Ouellette
M
M
D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D004270:DNA, Circular / Q000737:chemistry; D016054:DNA, Protozoan / Q000737:chemistry; D004351:Drug Resistance / Q000235:genetics; D005784:Gene Amplification; D007654:Ketoconazole / Q000494:pharmacology; D007891:Leishmania / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D009154:Mutation; D014162:Transfection
D000981:Antiprotozoal Agents; D004270:DNA, Circular; D016054:DNA, Protozoan; D000666:Amphotericin B; D007654:Ketoconazole