Laboratory of Pharmaceutical Microbiology, Ghent University, Harelbekestraat 72, B-9000, Ghent, Belgium.
Res Microbiol. 2010 May;161(4):284-92. doi: 10.1016/j.resmic.2010.02.004. Epub 2010 Feb 17.
Biofilm formation is often associated with persistent Candida albicans infections. Treatment of these infections is difficult, since sessile C. albicans cells show increased resistance towards antifungal agents. The molecular mechanisms behind biofilm resistance in C. albicans are not yet understood. In the present study, we investigated the transcriptional response in young and mature in vitro-grown biofilms after a short and longer exposure time to high doses of fluconazole or amphotericin B. Treatment of biofilms with high doses of antifungal agents resulted in a drug-specific transcriptional response. Exposure of biofilms to fluconazole induced upregulation of genes encoding enzymes involved in ergosterol biosynthesis (ERG1, ERG3, ERG11 and ERG25). Treatment of biofilms with amphotericin B resulted in an overexpression of KRE1 and SKN1, two genes encoding proteins involved in beta-1,6-glucan biosynthesis. Our data indicate that sessile C. albicans cells show controlled regulation of gene expression, as they quickly mount a drug-specific transcriptional response in the presence of high doses of antifungal agents. These transcriptional changes suggest upregulation of ergosterol biosynthesis (fluconazole) and upregulation of beta-1,6-glucan biosynthesis (amphotericin B) in sessile C. albicans cells that might contribute to a resistant biofilm phenotype.
生物膜的形成通常与持续性白色念珠菌感染有关。这些感染的治疗很困难，因为定殖的白色念珠菌细胞对抗真菌药物表现出更高的耐药性。白色念珠菌生物膜耐药性的分子机制尚不清楚。在本研究中，我们研究了短时间和长时间暴露于高剂量氟康唑或两性霉素 B 后，体外培养的年轻和成熟生物膜中的转录反应。用高剂量抗真菌药物处理生物膜会导致特定药物的转录反应。氟康唑处理生物膜会诱导与麦角固醇生物合成相关的基因（ERG1、ERG3、ERG11 和 ERG25）上调。两性霉素 B 处理生物膜会导致编码参与β-1,6-葡聚糖生物合成的蛋白质的 KRE1 和 SKN1 基因的过表达。我们的数据表明，定殖的白色念珠菌细胞表现出受控的基因表达调控，因为它们在存在高剂量抗真菌药物时会迅速产生特定药物的转录反应。这些转录变化表明，麦角固醇生物合成（氟康唑）和β-1,6-葡聚糖生物合成（两性霉素 B）的上调可能有助于形成耐药性生物膜表型。
