École Doctorale des Sciences de la Vie, Université Clermont Auvergne, Santé, Agronomie, Environnement, Clermont-Ferrand, France.
GenXPro GmbH, Frankfurt am Main, Germany.
Appl Environ Microbiol. 2019 Oct 16;85(21). doi: 10.1128/AEM.01370-19. Print 2019 Nov 1.
As for many opportunistic pathogens, the virulence potential of is highly heterogeneous between isolates and correlated, to some extent, with phylogeny and gene repertoires. In sharp contrast with copious data on intraspecies genome diversity, little is known about transcriptome diversity despite the role of complex genetic regulation in pathogenicity. The current study implemented RNA sequencing to characterize the transcriptome profiles of 33 isolates under optimal growth conditions. Transcript levels of conserved single-copy genes were comprehensively explored from several perspectives, including phylogeny, -predicted virulence category based on epidemiological multilocus sequence typing (MLST) data, and virulence phenotype assessed in Comparing baseline transcriptomes between isolates was intrinsically more complex than standard genome comparison because of the inherent plasticity of gene expression in response to environmental conditions. We show that the relevance of correlation analyses and their statistical power can be enhanced by using principal-component analysis to remove the first level of irrelevant, highly coordinated changes linked to growth phase. Our results highlight the major contribution of transcription factors with key roles in virulence to the diversity of transcriptomes. Divergence in the basal transcript levels of a substantial fraction of the transcriptome was observed between lineages I and II, echoing previously reported epidemiological differences. Correlation analysis with virulence identified numerous sugar metabolism-related genes, suggesting that specific pathways might play roles in the onset of infection in is a multifaceted bacterium able to proliferate in a wide range of environments from soil to mammalian host cells. The accumulated genomic data underscore the contribution of intraspecies variations in gene repertoire to differential adaptation strategies between strains, including infection and stress resistance. It seems very likely that the fine-tuning of the transcriptional regulatory network is also a key component of the phenotypic diversity, albeit more difficult to investigate than genome content. Some studies reported incongruity in the basal transcriptome between isolates, suggesting a putative relationship with phenotypes, but small isolate numbers hampered proper correlation analyses with respect to their characteristics. The present study is the embodiment of the promising approach that consists of analyzing correlations between transcriptomes and various isolate characteristics. Statistically significant correlations were found with phylogenetic groups, epidemiological evidence of virulence potential, and virulence in larvae used as an model.
就许多机会性病原体而言， 之间的毒力潜力在分离株之间高度异质，并且在某种程度上与系统发育和基因库相关。与种内基因组多样性的大量数据形成鲜明对比的是，尽管复杂的遗传调控在致病性中起作用，但对转录组多样性的了解甚少。本研究实施了 RNA 测序，以描述 33 株在最佳生长条件下的转录组谱。从几个角度全面探讨了保守单拷贝基因的转录水平，包括系统发育、基于流行病学多位点序列分型 (MLST) 数据预测的毒力类别，以及在 中评估的毒力表型。比较分离株之间的基线转录组本质上比标准基因组比较更为复杂，因为基因表达对环境条件的固有可塑性。我们表明，通过使用主成分分析去除与生长阶段相关的第一级不相关、高度协调的变化，可以增强相关性分析的相关性及其统计能力。我们的结果强调了转录因子在毒力多样性中的主要作用，转录因子在毒力多样性中起着关键作用。谱系 I 和 II 之间观察到大部分转录组的基础转录水平存在分歧，这与先前报道的流行病学差异相呼应。与 毒力的相关分析确定了许多糖代谢相关基因，表明特定途径可能在 感染的开始中起作用 是一种多面细菌，能够在从土壤到哺乳动物宿主细胞的广泛环境中增殖。积累的基因组数据强调了基因库中种内变异对菌株间差异适应策略的贡献，包括感染和应激抗性。精细调节转录调控网络似乎也是表型多样性的关键组成部分，尽管比基因组内容更难研究。一些研究报告了分离株之间的基础转录组不一致，这表明与表型存在潜在关系，但由于分离株数量较少，因此难以对其特征进行适当的相关分析。本研究体现了一种很有前途的方法，即分析转录组与各种分离株特征之间的相关性。与系统发育组、流行病学证据的毒力潜力以及 幼虫中的毒力发现了具有统计学意义的相关性，幼虫被用作 模型。
