Some Effects of Nystatin on the Growth of Four Aspergillus Species

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Abstract
At subinhibitory concentrations, nystatin exerted its main effect on four species of Aspergillus in the lag phase of growth. Subsequent growth and sporulation appeared to be normal, indicating the lack of permanent damage to survivors. Starting with an inoculum of spores the increased lag period was caused by the inhibition of swelling and germination; starting with an inoculum of mycelium, by the temporary cessation of hyphal elongation. At low concentrations of nystatin the lag period increased in proportion to the increase in initial nystatin concentration. Under these conditions the length of the lag was limited by the natural breakdown of the antibiotic in the medium rather than by any metabolic activity or adaptive response of the fungi. However, the lag period increased sharply, as the inhibitory nystatin concentration for each species was approached, to values greater than can be explained solely by the increased concentration of antibiotic. This was not due to the time taken for growth by any especially resistant spores but to the greatly decreased viability and slow outgrowth of normal survivors. This loss in viability was due to factors other than K+ leakage. Plasmolysis of germinated spores and mycelium occurred in some Aspergillus species at high concentrations of nystatin. The action of nystatin was relatively slow; no significant loss of viability or lengthening of the lag phase was noted until after exposure to the antibiotic for at least one hour, even at very high concentrations. Since the fungicidal effect on Aspergillus terreus and A. fumigatus was appreciably slower than on A. niger and A. flavus, it is possible that differences in the rate of absorption of nystatin in part determine sensitivity to nystatin. Spore germination took place at higher nystatin concentrations than did hyphal growth. The lethal dose for spores, which was three to four times higher than the fungistatic value, was also higher than for the mycelium.

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