Population genomics of drug resistance in Candida albicans
Population genomics of drug resistance in Candida albicans
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DOI：
10.1073/pnas.102291099
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发表时间：
2002-07-09
影响因子：
11.1
通讯作者：
Anderson, JB
中科院分区：
文献类型：
--
作者：
Cowen, LE;Nantel, A;Anderson, JB
我们遵循适应实验微生物种群的抗菌药物的抑制浓度。在所有情况下，耐药性的演变都伴随着基因表达的变化，这种变化在没有药物的情况下持续存在;新的基因表达模式是组成性的。在抗真菌药物氟康唑存在的情况下，致病真菌白色念珠菌的四个重复种群在330代进化过程中发生了基因表达的变化。超过5,000个ORF的全基因组表达谱鉴定了301个，其表达被显著调节。聚类分析确定了三种不同的基因表达模式的适应药物。一种模式是一个群体所独有的，包括多药ATP结合盒转运蛋白基因CDR 2的上调。第二种模式发生在三个种群的适应后期，其中两个种群在其进化的早期，观察到不同的模式在适应的早期阶段。继承的早期和晚期阶段的基因表达模式，其中包括多药主要促进转运基因，MDR 1的上调，必须代表一个共同的程序，适应这种抗真菌药物。这三种基因表达模式也在氟康唑耐药的临床分离株中得到了鉴定，进一步证明了这些模式代表了对氟康唑适应的共同程序。
We followed adaptation in experimental microbial populations to inhibitory concentrations of an antimicrobial drug. The evolution of drug resistance was accompanied in all cases by changes in gene expression that persisted in the absence of the drug; the new patterns of gene expression were constitutive. The changes in gene expression occurred in four replicate populations of the pathogenic fungus Candida albicans during 330 generations of evolution in the presence of the antifungal drug fluconazole. Genome-wide expression profiling of over 5,000 ORFs identified 301 whose expression was significantly modulated. Cluster analysis identified three distinct patterns of gene expression underlying adaptation to the drug. One pattern was unique to one population and included up-regulation of the multidrug ATP-binding cassette transporter gene, CDR2. A second pattern occurred at a late stage of adaptation in three populations; for two of these populations profiled earlier in their evolution, a different pattern was observed at an early stage of adaptation. The succession of early- and late-stage patterns of gene expression, both of which include up-regulation of the multidrug major facilitator transporter gene, MDR1, must represent a common program of adaptation to this antifungal drug. The three patterns of gene expression were also identified in fluconazole-resistant clinical isolates, providing further evidence that these patterns represent common programs of adaptation to fluconazole.