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Proteomic and transcriptomic analysis of Microviridae φX174 infection reveals broad up-regulation of host membrane damage and heat shock responses
bioRxiv - Microbiology Pub Date : 2020-10-26 , DOI: 10.1101/2020.10.26.355149
Bradley W Wright , Dominic Y Logel , Mehdi Mirzai , Dana Pascovici , Mark P Molloy , Paul R Jaschke

Measuring host-bacteriophage dynamics is an important approach to understanding bacterial survival functions and responses to infection. The model Microviridae bacteriophage φX174 is endemic to the human gut and has been studied for over seventy years but the host response to infection has never been investigated in detail. To address this gap in our understanding of this important interaction within our microbiome we have measured host Escherichia coli C proteomic and transcriptomic response to φX174 infection. We used mass spectrometry and RNA-seq to identify and quantify all 11 φX174 proteins and over 1,700 E. coli proteins, enabling us to comprehensively map host pathways involved in φX174 infection. Most notably, we see significant host responses centered on membrane damage and remodeling, cellular chaperone and translocon activity, and lipoprotein processing, which we speculate is due to the peptidoglycan-disruptive effects of the φX174 lysis protein E on MraY activity. We also observe the massive upregulation of small heat-shock proteins IbpA/B, along with other heat shock pathway chaperones, and speculate on how the specific characteristics of holdase protein activity may be beneficial for viral infections. Together, this study enables us to begin to understand the proteomic and transcriptomic host responses of E. coli to Microviridae infections and contributes insights to the activities of this important model phage.

中文翻译:

蛋白质组学和转录组学分析表明,微病毒科菌φX174感染显示宿主膜损伤和热休克反应的广泛上调

测量宿主噬菌体动力学是了解细菌存活功能和对感染的反应的重要方法。Microviridae噬菌体模型φX174是人类肠道特有的,已经研究了70多年,但从未详细研究宿主对感染的反应。为了解决我们对微生物组内部这一重要相互作用的理解的空白,我们测量了宿主对φX174感染的大肠杆菌C蛋白质组和转录组反应。我们使用质谱和RNA序列来鉴定和定量所有11种φX174蛋白和1,700多种大肠杆菌蛋白质,使我们能够全面定位涉及φX174感染的宿主途径。最值得注意的是,我们发现明显的宿主反应集中在膜损伤和重塑,细胞伴侣和translocon活性以及脂蛋白加工上,我们推测这是由于φX174裂解蛋白E对MraY活性的肽聚糖破坏作用所致。我们还观察到小热休克蛋白IbpA / B以及其他热激途径分子伴侣的大量上调,并推测保持酶蛋白活性的特定特征如何可能对病毒感染有益。在一起,这项研究使我们能够开始理解大肠杆菌微病毒科的蛋白质组和转录组宿主反应 感染并为这种重要的噬菌体模型的活动提供见解。
更新日期:2020-10-27
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