An integrated multi-omics analysis of identifies distinct molecular characteristics in pulmonary infections of Pseudomonas aeruginosa.

IF 6.7 1区 医学 Q1 Immunology and Microbiology
PLoS Pathogens Pub Date : 2023-08-29 eCollection Date: 2023-08-01 DOI:10.1371/journal.ppat.1011570
Yang Yang, Teng Ma, Jun Zhang, Yu Tang, Miao Tang, Chaoyu Zou, Yige Zhang, Mingbo Wu, Xueli Hu, Huan Liu, Qianhua Zhang, Yilin Liu, Hongliang Li, Jing Shirley Li, Zhuochong Liu, Jing Li, Taiwen Li, Xikun Zhou
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引用次数: 0

Abstract

Pseudomonas aeruginosa (P. aeruginosa) can cause severe acute infections, including pneumonia and sepsis, and cause chronic infections, commonly in patients with structural respiratory diseases. However, the molecular and pathophysiological mechanisms of P. aeruginosa respiratory infection are largely unknown. Here, we performed assays for transposase-accessible chromatin using sequencing (ATAC-seq), transcriptomics, and quantitative mass spectrometry-based proteomics and ubiquitin-proteomics in P. aeruginosa-infected lung tissues for multi-omics analysis, while ATAC-seq and transcriptomics were also examined in P. aeruginosa-infected mouse macrophages. To identify the pivotal factors that are involved in host immune defense, we integrated chromatin accessibility and gene expression to investigate molecular changes in P. aeruginosa-infected lung tissues combined with proteomics and ubiquitin-proteomics. Our multi-omics investigation discovered a significant concordance for innate immunological and inflammatory responses following P. aeruginosa infection between hosts and alveolar macrophages. Furthermore, we discovered that multi-omics changes in pioneer factors Stat1 and Stat3 play a crucial role in the immunological regulation of P. aeruginosa infection and that their downstream molecules (e.g., Fas) may be implicated in both immunosuppressive and inflammation-promoting processes. Taken together, these findings indicate that transcription factors and their downstream signaling molecules play a critical role in the mobilization and rebalancing of the host immune response against P. aeruginosa infection and may serve as potential targets for bacterial infections and inflammatory diseases, providing insights and resources for omics analyses.

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铜绿假单胞菌肺部感染的综合多组学分析确定了不同的分子特征。
铜绿假单胞菌(P.aeruginosa)可引起严重的急性感染,包括肺炎和败血症,并可引起慢性感染,常见于结构性呼吸道疾病患者。然而,铜绿假单胞菌呼吸道感染的分子和病理生理机制在很大程度上是未知的。在这里,我们在铜绿假单胞菌感染的肺组织中使用测序(ATAC-seq)、转录组学和基于定量质谱的蛋白质组学和泛素蛋白质组学进行了转座酶可及染色质的测定,以进行多组学分析,同时在铜绿假单孢菌感染的小鼠巨噬细胞中也检测了ATAC-seq和转录组学。为了确定参与宿主免疫防御的关键因素,我们结合染色质可及性和基因表达,结合蛋白质组学和泛素蛋白质组学研究铜绿假单胞菌感染肺组织的分子变化。我们的多组学研究发现,宿主和肺泡巨噬细胞感染铜绿假单胞菌后,先天免疫和炎症反应显著一致。此外,我们发现先驱因子Stat1和Stat3的多组学变化在铜绿假单胞菌感染的免疫调节中起着至关重要的作用,它们的下游分子(如Fas)可能参与免疫抑制和炎症促进过程。总之,这些发现表明,转录因子及其下游信号分子在宿主对铜绿假单胞菌感染的免疫反应的动员和再平衡中发挥着关键作用,并可能成为细菌感染和炎症性疾病的潜在靶点,为组学分析提供了见解和资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
PLoS Pathogens
PLoS Pathogens 生物-病毒学
CiteScore
11.40
自引率
3.00%
发文量
598
审稿时长
2 months
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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