Suzuki Shingo, Horinouchi Takaaki, Furusawa Chikara
Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
Nat Commun. 2014 Dec 17;5:5792. doi: 10.1038/ncomms6792.
Although many mutations contributing to antibiotic resistance have been identified, the relationship between the mutations and the related phenotypic changes responsible for the resistance has yet to be fully elucidated. To better characterize phenotype-genotype mapping for drug resistance, here we analyse phenotypic and genotypic changes of antibiotic-resistant Escherichia coli strains obtained by laboratory evolution. We demonstrate that the resistances can be quantitatively predicted by the expression changes of a small number of genes. Several candidate mutations contributing to the resistances are identified, while phenotype-genotype mapping is suggested to be complex and includes various mutations that cause similar phenotypic changes. The integration of transcriptome and genome data enables us to extract essential phenotypic changes for drug resistances.
尽管已经鉴定出许多导致抗生素耐药性的突变，但这些突变与耐药性相关的表型变化之间的关系尚未完全阐明。为了更好地表征耐药性的表型-基因型图谱，我们在此分析了通过实验室进化获得的抗生素耐药性大肠杆菌菌株的表型和基因型变化。我们证明，耐药性可以通过少数基因的表达变化进行定量预测。鉴定出了几个导致耐药性的候选突变，同时表明表型-基因型图谱很复杂，包括各种导致相似表型变化的突变。转录组和基因组数据的整合使我们能够提取出耐药性的基本表型变化。
