Polyene antibiotics are toxic towards eukaryotic cells such as fungi, algae, protozoa,
and mammalian cells, but not toxic towards prokaryotic cells such as bacteria. It is now
generally accepted that the polyene molecules combine with membrane sterols to yield a
complex, as a result of which the cell membrane can no longer function as a selective
restraning barrier. Dam-age to the membrane results in a cell death due to a leakage of
many cell constituents.
However the mutants insensitive to the polyene antibiotics are occasionally isolated
from sensitive strains of many fungi both in vivo and in vitro. Mutants of Aspergillus
funneliae resistant to relatively high level of amphotericin B and low level of nystatin,
obtained by successive transfers of wild type in the presence of increasing
concentrations of the polyenes, showed quantitatively and qualitatively altered sterol
compositions, as compared with that of wild hypes. Former mutant produced a large
amount of 7, 22, 24(28) -ergostatrien·3β-ol and a lesser amount of
7, 22 -ergostadien-3β-ol while the latter mutant produced not only
these two sterols but also ergosterol, which is a major sterol of wild types. This
phenomenon has also been demon-strated in the polyene resistant mutants of
Cryptococcus neoformans whose sterol compositions are different according to the level
of resistance to the polyenes. While the high level resistant mutants produced
ergostatrien-3β-ol and 4"-ergosten-3β-ol the low level resistant mutants produced J
5, 8, 22 -ergostadien-3β-ol and 8-ergosten-3β-ol. These
results suggest that the effectiveness of polyene bindings is in the order: 5,
7, 7- and 8-sterol. This order also seems to be
true to the impairments of many other properties, relevant to sterols, of both fungi.
However as the mutants resistant to amphotericin B of C. neoformans are exclusive
from those mutants due to the altered sterol compositions of the cells, the sterol change
is not an only mechanism of resistance to the polyenes.
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