Anti-Candida activity of polyoxin: example of peptide transport in yeasts

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Abstract
The polyoxins, nucleoside peptide antibiotics, are effective inhibitors of chitin synthesis in some fungi and yeasts. Although isolated chitin synthetases appear to be equally sensitive to inhibition by polyoxins, intact yeast cells are relatively insensitive. It has been suggested that polyoxins enter cells by a peptide carrier transport mechanism. In this paper, we report results which demonstrate that changes in the growth conditions significantly affect the degree of sensitivity of Canidida albicans to the polyoxins. For example, a minimal inhibitory concentration of 0.1 micrograms/ml was obtained in a defined medium compared with a minimal inhibitory concentration of 1,000 micrograms/ml with conventional media. Various noninhibitory di- and tripeptides, when added to the media, were found to antagonize the anti-Candida activity of polyoxins. In addition, polyoxin-resistant mutants of C. albicans were shown to exhibit cross-resistance with other dipeptide antibiotics. The data reported herein support peptide transport of polyoxins in C. albicans.