Quantitative proteomic analysis of host--pathogen interactions: a study of Acinetobacter baumannii responses to host airways.
Quantitative proteomic analysis of host--pathogen interactions: a study of Acinetobacter baumannii responses to host airways.
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DOI：
10.1186/s12864-015-1608-z
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发表时间：
2015-05-30
期刊：
影响因子：
4.4
通讯作者：
Bou G
中科院分区：
文献类型：
--
作者：
Méndez JA;Mateos J;Beceiro A;Lopez M;Tomás M;Poza M;Bou G
鲍曼不动杆菌是一个主要的健康问题。鲍曼不动杆菌引起的最常见感染是医院获得性肺炎，相关死亡率约为50%。在鲍曼不动杆菌引起的肺炎中，既没有在体内也没有在体外进行蛋白质组学或转录组学水平的表达谱分析。在这项研究中，我们在模拟气道中发现的条件下表征了鲍曼不动杆菌的蛋白质组，以深入了解鲍曼不动杆菌如何适应宿主，并提高对这种细菌的发病机制和毒力的认识。在不同的条件下培养鲍曼不动杆菌临床菌株：在感染大鼠支气管肺泡灌洗液存在的情况下，在模拟呼吸道条件和对照条件下使用RAW 264.7细胞。我们使用iTRAQ标记和LC-MALDI-TOF/TOF来研究鲍曼不动杆菌对巨噬细胞/半胱氨酸暴露的反应。179个蛋白有差异表达。在两种模型中，参与以下过程的蛋白都过表达：(i)发病机制和毒力（OmpA, YjjK）；（ii）细胞壁/膜/包膜生物发生（MurC）；（iii）能量生产和转化（乙酰辅酶a水解酶）；（iv）翻译（50S核糖体蛋白L9）。以下涉及的蛋白质表达不足：(i)脂质代谢（短链脱氢酶）；（ii）氨基酸代谢和转运（天冬氨酸转氨酶）；（iii）功能未知（dna结合蛋白）；无机离子转运和代谢（氢过氧化物酶）。我们观察到细胞壁合成的改变，并在两种离体模型（OmpA和YjjK）中鉴定出2种与bbbb15肽/蛋白相关的毒力相关蛋白上调，这表明这些蛋白是气道发病和毒力的基础。该研究是鲍曼不动杆菌离体蛋白质组的首次全面概述，是确定鲍曼不动杆菌引起的肺炎的诊断生物标志物、新药物靶点和潜在候选疫苗的重要一步。本文的在线版本（doi:10.1186/s12864-015-1608-z）包含补充材料，可供授权用户使用。
Acinetobacter baumannii is a major health problem. The most common infection caused by A. baumannii is hospital acquired pneumonia, and the associated mortality rate is approximately 50 %. Neither in vivo nor ex vivo expression profiling has been performed at the proteomic or transcriptomic level for pneumonia caused by A. baumannii. In this study, we characterized the proteome of A. baumannii under conditions that simulate those found in the airways, to gain some insight into how A. baumannii adapts to the host and to improve knowledge about the pathogenesis and virulence of this bacterium. A clinical strain of A. baumannii was grown under different conditions: in the presence of bronchoalveolar lavage fluid from infected rats, of RAW 264.7 cells to simulate conditions in the respiratory tract and in control conditions. We used iTRAQ labelling and LC-MALDI-TOF/TOF to investigate how A. baumannii responds on exposure to macrophages/BALF. 179 proteins showed differential expression. In both models, proteins involved in the following processes were over-expressed: (i) pathogenesis and virulence (OmpA, YjjK); (ii) cell wall/membrane/envelope biogenesis (MurC); (iii) energy production and conversion (acetyl-CoA hydrolase); and (iv) translation (50S ribosomal protein L9). Proteins involved in the following were under-expressed: (i) lipid metabolism (short-chain dehydrogenase); (ii) amino acid metabolism and transport (aspartate aminotransferase); (iii) unknown function (DNA-binding protein); and (iv) inorganic ion transport and metabolism (hydroperoxidase). We observed alterations in cell wall synthesis and identified 2 upregulated virulence-associated proteins with >15 peptides/protein in both ex vivo models (OmpA and YjjK), suggesting that these proteins are fundamental for pathogenesis and virulence in the airways. This study is the first comprehensive overview of the ex vivo proteome of A. baumannii and is an important step towards identification of diagnostic biomarkers, novel drug targets and potential vaccine candidates in the fight against pneumonia caused by A. baumannii. The online version of this article (doi:10.1186/s12864-015-1608-z) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
Bigot, Armelle;Botton, Eleonore;Charbit, Alain
通讯作者：
Charbit, Alain
影响因子：
3.4
作者：
Choi, CH;Lee, EY;Lee, JC
通讯作者：
Lee, JC
影响因子：
2.1
作者：
Eijkelkamp, Bart A.;Stroeher, Uwe H.;Brown, Melissa H.
通讯作者：
Brown, Melissa H.
影响因子：
4.4
作者：
Gayoso, Carmen M.;Mateos, Jesus;Bou, German
通讯作者：
Bou, German
影响因子：
8
作者：
Emanuele, JJ;Jin, HY;Villafranca, JJ
通讯作者：
Villafranca, JJ