Mapping the Transcriptional and Fitness Landscapes of a Pathogenic E. coli Strain: The Effects of Organic Acid Stress under Aerobic and Anaerobic Conditions.
Mapping the Transcriptional and Fitness Landscapes of a Pathogenic E. coli Strain: The Effects of Organic Acid Stress under Aerobic and Anaerobic Conditions.
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DOI：
10.3390/genes12010053
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发表时间：
2020-12-31
期刊：
影响因子：
3.5
通讯作者：
Lund PA
中科院分区：
文献类型：
--
作者：
Bushell F;Herbert JMJ;Sannasiddappa TH;Warren D;Turner AK;Falciani F;Lund PA
有几种方法可用于在全基因组水平上探测细胞对外部应激的反应。 RNAseq 可用于测量暴露于压力后所有基因表达的变化，但没有提供有关这些基因对生物体在压力下生存的能力的贡献的信息。基因组中每个非必需基因对生物体在应激下的适应性的相对贡献可以通过使用测序来估计在不同条件下生长的密集转座子文库的成员频率的方法来获得，例如通过转座子定向插入测序（TraDIS）。因此，这两种方法探讨了生物体基础生物学的不同方面。我们有兴趣确定这两种方法的数据在相关基因和途径上的收敛程度。为此，我们研究了具有生物学意义的压力的组合。人类肠道含有通过碳化合物发酵产生的不同有机短链脂肪酸（SCFA），大肠杆菌在通过肠道时会接触到这些脂肪酸。它们的影响可能取决于环境 pH 值和氧气含量。因此，我们生成了尿路致病性大肠杆菌菌株的 RNAseq 和 TraDIS 数据，该菌株在 pH 7 或 pH 5.5 下，在存在或不存在三种 SCFA（乙酸、丙酸和丁酸）的情况下（需氧或厌氧）生长。我们的分析确定已知的和新颖的途径在这些条件下可能很重要。基因表达和适应度之间不存在简单的相关性，但我们发现 KEGG 通路存在显着重叠，在对两种方法的数据进行分析后，这些通路预计会丰富，并且其中大多数显示出适应度特征，可以从基因表达数据中预测出适应度特征，假设表达具有适应性。发现不在大肠杆菌核心基因组中的基因特别有可能表现出表达水平和对健康的贡献之间的正相关性。
Several methods are available to probe cellular responses to external stresses at the whole genome level. RNAseq can be used to measure changes in expression of all genes following exposure to stress, but gives no information about the contribution of these genes to an organism’s ability to survive the stress. The relative contribution of each non-essential gene in the genome to the fitness of the organism under stress can be obtained using methods that use sequencing to estimate the frequencies of members of a dense transposon library grown under different conditions, for example by transposon-directed insertion sequencing (TraDIS). These two methods thus probe different aspects of the underlying biology of the organism. We were interested to determine the extent to which the data from these two methods converge on related genes and pathways. To do this, we looked at a combination of biologically meaningful stresses. The human gut contains different organic short-chain fatty acids (SCFAs) produced by fermentation of carbon compounds, and Escherichia coli is exposed to these in its passage through the gut. Their effect is likely to depend on both the ambient pH and the level of oxygen present. We, therefore, generated RNAseq and TraDIS data on a uropathogenic E. coli strain grown at either pH 7 or pH 5.5 in the presence or absence of three SCFAs (acetic, propionic and butyric), either aerobically or anaerobically. Our analysis identifies both known and novel pathways as being likely to be important under these conditions. There is no simple correlation between gene expression and fitness, but we found a significant overlap in KEGG pathways that are predicted to be enriched following analysis of the data from the two methods, and the majority of these showed a fitness signature that would be predicted from the gene expression data, assuming expression to be adaptive. Genes which are not in the E. coli core genome were found to be particularly likely to show a positive correlation between level of expression and contribution to fitness.
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影响因子：
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通讯作者：
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Cronan, John E
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