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编码一种免疫原性乙醇脱氢酶的白色念珠菌ADH1基因的结构与调控

Structure and regulation of the Candida albicans ADH1 gene encoding an immunogenic alcohol dehydrogenase.

作者信息

Bertram G, Swoboda R K, Gooday G W, Gow N A, Brown A J

机构信息

University of Aberdeen, Marischal College, U.K.

出版信息

Yeast. 1996 Feb;12(2):115-27. doi: 10.1002/(sici)1097-0061(199602)12:2<115::aid-yea889>3.0.co;2-e.

DOI:10.1002/(sici)1097-0061(199602)12:2<115::aid-yea889>3.0.co;2-e
PMID:8686375
Abstract

The Candida albicans ADH1 gene encodes an alcohol dehydrogenase which is immunogenic during infections in humans. The ADH1 gene was isolated and sequenced, and the 5'- and 3'-ends of its mRNA were mapped. The gene encodes a 350 amino acid polypeptide with strong homology (70.5-85.2% identity) to alcohol dehydrogenases from Saccharomyces cerevisiae, Kluyveromyces lactis and Schizosaccharomyces pombe. The cloned C. albicans ADH1 gene was shown to be functional through complementation of adh mutations and efficient production of active alcohol dehydrogenase in S. cerevisiae. Northern analysis of C. albicans RNA revealed that ADH1 mRNA levels were regulated in response to carbon source and during batch growth. During growth on glucose, ADH1 mRNA levels rose to maximum levels during late exponential growth phase and declined to low levels in stationary phase. The ADH1 mRNA was relatively abundant during growth on galactose, glycerol, pyruvate, lactate or succinate, and less abundant during growth on glucose or ethanol. Alcohol dehydrogenase levels did not correlate closely with ADH1 mRNA levels under the growth conditions studied, suggesting either that this locus is controlled at both transcriptional and post-transcriptional levels, or that other differentially regulated ADH loci exist in C. albicans.

摘要

白色念珠菌ADH1基因编码一种乙醇脱氢酶,该酶在人类感染过程中具有免疫原性。分离并测定了ADH1基因的序列,并绘制了其mRNA的5′端和3′端图谱。该基因编码一个350个氨基酸的多肽,与酿酒酵母、乳酸克鲁维酵母和粟酒裂殖酵母的乙醇脱氢酶具有高度同源性(同一性为70.5 - 85.2%)。通过对adh突变体的互补作用以及在酿酒酵母中高效产生活性乙醇脱氢酶,证明克隆的白色念珠菌ADH1基因具有功能。对白色念珠菌RNA的Northern分析表明,ADH1 mRNA水平在碳源响应和分批培养过程中受到调节。在葡萄糖上生长时,ADH1 mRNA水平在指数生长后期升至最高水平,在稳定期降至低水平。在半乳糖、甘油、丙酮酸、乳酸或琥珀酸上生长时,ADH1 mRNA相对丰富,而在葡萄糖或乙醇上生长时则较少。在所研究的生长条件下,乙醇脱氢酶水平与ADH1 mRNA水平没有密切相关性,这表明该基因座要么在转录和转录后水平均受到调控,要么白色念珠菌中存在其他差异调节的ADH基因座。

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