Relationship Between Polyene Resistance and Sterol Compositions in Cryptococcus Neoformans

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Six mutants of Cryptococcus neoformans resistant to nystatin and pimaricin and three mutants resistant to amphotericin B were isolated by ultraviolet irradiation techniques from two wild-type strains. The major sterols of the wild-type strains were Δ7-ergosten-3β-ol and ergosterol. All six mutants resistant to nystatin and pimaricin showed either loss of ergosterol and concurrent production of Δ7, 22-ergostadien-3β-ol and Δ7-ergosten-3β-ol, or loss of both the wild-type sterols, with production of Δ8(9)-ergosten-3β-ol and Δ5, 8(9), 22-ergostatrien-3β-ol. The mutants producing Δ7, 22-ergostadien-3β-ol and Δ7-ergosten-3β-ol showed relatively low levels of resistance to nystatin and pimaricin, whereas the mutants producing Δ8(9)-ergosten-3β-ol and Δ5, 8(0), 22-ergostatrien-3β-ol showed a high level of resistance to either drug. Although highly resistant to amphotericin B, however, the three mutants produced sterol compositions identical to those of the wild types, indicating that the strains acquired resistance other than by alteration of the membrane sterols. The mutants producing Δ8(9) and Δ5, 8(9), 22 sterols were not virulent for mice, showed reduced growth rates at 25 C, and failed to grow at 37 C. The other mutants showed a slightly reduced rate of growth both at 25 and 37 C, and the virulence in mice was slightly reduced in comparison with that of the wild types. These comparisons were on gross observations and were not statistically analyzed.

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