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Exploring Listeria monocytogenes Transcriptomes in Correlation with Divergence of Lineages and Virulence as Measured in Galleria mellonella

机译:探索单核细胞增生李斯特菌转录组与谱系差异和毒力的相关性,如在 Galleria mellonella 中测量的那样

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摘要

As for many opportunistic pathogens, the virulence potential of Listeria monocytogenes 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 in vitro growth conditions. Transcript levels of conserved single-copy genes were comprehensively explored from several perspectives, including phylogeny, in silico-predicted virulence category based on epidemiological multilocus sequence typing (MLST) data, and in vivo virulence phenotype assessed in Galleria mellonella. 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 in vivo virulence identified numerous sugar metabolism-related genes, suggesting that specific pathways might play roles in the onset of infection in G. mellonella.
机译:与许多机会性病原体一样,单核细胞增生李斯特菌的毒力潜力在分离株之间具有高度异质性,并在一定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着重要作用,但人们对转录组多样性知之甚少。本研究实施了RNA测序,以表征33个分离株在最佳体外生长条件下的转录组图谱。从系统发育、基于流行病学多位点序列分型(MLST)数据的计算机预测毒力类别以及Galleria mellonella中评估的体内毒力表型等多个角度全面探索保守单拷贝基因的转录水平。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来消除与生长阶段相关的第一级不相关的、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。我们的研究结果强调了在毒力中起关键作用的转录因子对转录组多样性的主要贡献。在谱系 I 和 II 之间观察到很大一部分转录组的基础转录水平存在差异,这与先前报道的流行病学差异相呼应。与体内毒力的相关性分析鉴定了许多糖代谢相关基因,表明特定途径可能在梅洛内拉感染的发生中发挥作用。

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