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基于血液应答调控子的蛋白质组学分析鉴定出一种新型的 III 型分泌系统必需底物。

Omics Analysis of Blood-Responsive Regulon in Identifies a Novel Essential T3SS Substrate.

机构信息

Laboratory of Post-Transcriptional Control of Gene Expression, Institute of Microbiology of the Czech Academy of Sciences, 14220 Prague, Czech Republic.

出版信息

Int J Mol Sci. 2021 Jan 13;22(2):736. doi: 10.3390/ijms22020736.

Abstract

Bacterial pathogens sense specific cues associated with different host niches and integrate these signals to appropriately adjust the global gene expression. is a Gram-negative, strictly human pathogen of the respiratory tract and the etiological agent of whooping cough (pertussis). Though does not cause invasive infections, previous results indicated that this reemerging pathogen responds to blood exposure. Here, omics RNA-seq and LC-MS/MS techniques were applied to determine the blood-responsive regulon of . These analyses revealed that direct contact with blood rewired global gene expression profiles in as the expression of almost 20% of all genes was significantly modulated. However, upon loss of contact with blood, the majority of blood-specific effects vanished, with the exception of several genes encoding the T3SS-secreted substrates. For the first time, the T3SS regulator BtrA was identified in culture supernatants of . Furthermore, proteomic analysis identified BP2259 protein as a novel secreted T3SS substrate, which is required for T3SS functionality. Collectively, presented data indicate that contact with blood represents an important cue for cells.

摘要

细菌病原体感知与不同宿主小生境相关的特定线索,并整合这些信号,以适当调整全局基因表达。百日咳杆菌是一种革兰氏阴性、严格的呼吸道人类病原体,也是百日咳(百日咳)的病原体。虽然百日咳杆菌不会引起侵袭性感染,但先前的结果表明,这种重新出现的病原体对血液暴露有反应。在这里,应用组学 RNA-seq 和 LC-MS/MS 技术来确定百日咳杆菌的血液反应调节子。这些分析表明,血液的直接接触重新布线了 中全局基因表达谱,因为几乎所有基因的表达都被显著调节。然而,一旦失去与血液的接触,除了几个编码 T3SS 分泌底物的基因外,大多数血液特异性效应消失。首次在百日咳杆菌的培养上清液中鉴定到 T3SS 调节因子 BtrA。此外,蛋白质组学分析鉴定出 BP2259 蛋白为一种新型分泌 T3SS 底物,该底物对于 T3SS 功能是必需的。总之,目前的数据表明,血液接触代表了百日咳杆菌细胞的一个重要线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb00/7828420/f885561abff5/ijms-22-00736-g001.jpg

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