Journal of Antimicrobial Chemotherapy (2002) 49, 905-915
© 2002 The British Society for Antimicrobial Chemotherapy
Response of gene expression in Saccharomyces cerevisiae to amphotericin B and nystatin measured by microarrays
1Department of Biological Science and Biotechnology, and 2State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084; 3Beijing National Biochip Research & Engineering Center, Jia 2 Qinghua West Road, Beijing 100084, People’s Republic of China
Received 7 September 2001; returned 18 November 2001; revised 14 December 2001; accepted 4 January 2002.
The response of the yeast Saccharomyces cerevisiae to two polyene antibiotics, amphotericin B and nystatin, was studied by genomic expression profiling. The two agents produced highly similar expression pattern changes, which was consistent with their known identical mechanisms of action on cell membranes. Detailed analysis was focused on the amphotericin B-treated sample in this study. Our data showed that genes involved in mitochondrial ribosomal protein synthesis were more severely repressed than those in the cytoplasm, which might contribute to the cytotoxicity of amphotericin B. To counteract the leakage of intracellular nutrients and ions from the pores in the cell membrane caused by amphotericin B, c. 17 genes involved in transport facilitation were induced, presumably to allow more efficient uptake of nutrients and ions. The expression level of five genes involved in ergosterol synthesis dropped and three genes related to cell wall biogenesis were induced, indicating that the cell membrane and cell wall were also affected by the presence of polyene antibiotics. It was observed that the pleiotropic drug resistance network in yeast cells was activated after exposure to amphotericin B, possibly contributing to the acquisition of amphotericin B resistance. Part of the gene expression alteration measured by microarray was confirmed by quantitative RT–PCR.
* Corresponding author. Tel: +86-10-62773059; Fax: +86-10-62566806; E-mail: jcheng{at}tsinghua.edu.cn
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