ACRIFLAVIN RESISTANCE IN THE HEMOFLAGELLATE, LEISHMANIA TARENTOLAE

Abstract

The accumulation, metabolism, and distribution of acriflavin (acr) in two culture strains of Leishmania tarentolae were studied . One strain, reported previously, was sensitive to the dye, i .e . became dyskinetoplastic and could not be subcultured in the presence of 470 ng/ml acr, and one was resistant . Accumulation was studied by fluorescence of the dye within cells and by uptake of acr-3 H by cells . Metabolism was studied by paper chromatography of aqueous extracts from cells grown with acr-3 H, and distribution was examined by fluorescence and quantitative electron microscope radioautography . Substances affecting the response to acr included heroin and an acr-sensitizing factor initially obtained from red cells but here shown to be distinct from hemoglobin . In the presence of the sensitizing factor or in the absence of hemin, the resistant strain became dyskinetoplastic and could not be subcultured . Acr fluorescence appeared in the nucleus of the resistant strain, and the percentage of radioautography grains appearing in the nucleus increased . Under these conditions the distribution of radioactivity from chromatographed extracts was altered from the normal in a similar fashion .

Drug-Resistant Leptomonas : Cross-Resistance in Trypanocide-Resistant Clones

“…Trypanosomatidae thus provide a parallel to yeasts: some yeasts grow as petites despite almost total elimination of mitochondrial function; others either cannot form petites or cannot be so maintained (6,7). Thus the induction of an acriflavin-resistant strain ofLeishmania tarentolae, surviving amid the appearance of unsubculturable dyskinetoplastic forms (18), might be construed as evidence that L. tarentolae behaves almost as a petite positive. Unfortunately, the absence of means of genetic recombination in trypanosomatidae precludes genetic analysis.…”

Effects of Ethidium Bromide and Several Acridine Dyes on the Kinetoplast DNA of Leishmania tropica*†

“…There seems to be a difference among the genera, with Leishmania being the most sensitive followed by Trypanosoma; Crithidia appears to be the least sensitive genus. Recently a strain of L. tarentolae resistant to acriflavin was reported by Strauss (47). The importance of the culture medium also cannot be overlooked in considering the relative drug sensitivities.…”