Response of gene expression in Saccharomyces cerevisiae to amphotericin B and nystatin measured by microarrays.
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.
Zhang
Liang
L
Department of Biological Science and Biotechnology, State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, People's Republic of China.
Zhang
Yan
Y
Zhou
Yiming
Y
An
Shuang
S
Zhou
Yuxiang
Y
Cheng
Jing
J
D000666:Amphotericin B / Q000494:pharmacology*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects* / Q000502:physiology; D009761:Nystatin / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism
D009761:Nystatin; D000666:Amphotericin B