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脂蛋白 CagT 和 Lpp20 的脂肪酸。

Fatty acids of lipoproteins CagT and Lpp20.

机构信息

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Vanderbilt Institute for Infection Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

出版信息

Microbiol Spectr. 2024 May 2;12(5):e0047024. doi: 10.1128/spectrum.00470-24. Epub 2024 Mar 19.

Abstract

Bacterial lipoproteins are post-translationally modified by the addition of acyl chains that anchor the protein to bacterial membranes. This modification includes two ester-linked and one amide-linked acyl chain on lipoproteins from Gram-negative bacteria. lipoproteins have important functions in pathogenesis (including delivering the CagA oncoprotein to mammalian cells) and are recognized by host innate and adaptive immune systems. The number and variety of acyl chains on lipoproteins impact the innate immune response through Toll-like receptor 2. The acyl chains added to lipoproteins are derived from membrane phospholipids. membrane phospholipids have previously been shown to consist primarily of C14:0 and C19:0 cyclopropane-containing acyl chains. However, the acyl composition of lipoproteins has not been determined. In this study, we characterized the acyl composition of two representative lipoproteins, Lpp20 and CagT. Fatty acid methyl esters were prepared from both purified lipoproteins and analyzed by gas chromatography-mass spectrometry. For comparison, we also analyzed phospholipids. Consistent with previous studies, we observed that the phospholipids contain primarily C14:0 and C19:0 cyclopropane-containing fatty acids. In contrast, both the ester-linked and amide-linked fatty acids found in lipoproteins were observed to be almost exclusively C16:0 and C18:0. A discrepancy between the acyl composition of membrane phospholipids and lipoproteins as reported here for has been previously reported in other bacteria including and . We discuss possible mechanisms.IMPORTANCEColonization of the stomach by is an important risk factor in the development of gastric cancer, the third leading cause of cancer-related death worldwide. persists in the stomach despite an immune response against the bacteria. Recognition of lipoproteins by TLR2 contributes to the innate immune response to . However, the role of lipoproteins in bacterial persistence is poorly understood. As the host response to lipoproteins depends on the acyl chain content, defining the acyl composition of lipoproteins is an important step in characterizing how lipoproteins contribute to persistence.

摘要

细菌脂蛋白通过添加酰基链进行翻译后修饰,这些酰基链将蛋白锚定在细菌膜上。革兰氏阴性菌的脂蛋白上有两种酯键连接和一种酰胺键连接的酰基链。脂蛋白在发病机制中具有重要功能(包括将 CagA 癌蛋白递送到哺乳动物细胞),并被宿主固有和适应性免疫系统识别。脂蛋白上酰基链的数量和种类通过 Toll 样受体 2 影响固有免疫反应。添加到脂蛋白上的酰基链来自膜磷脂。先前的研究表明,膜磷脂主要由 C14:0 和 C19:0 环丙烷含酰基链组成。然而,脂蛋白的酰基组成尚未确定。在这项研究中,我们对两种代表性脂蛋白 Lpp20 和 CagT 的酰基组成进行了表征。从纯化的脂蛋白中制备脂肪酸甲酯,并通过气相色谱-质谱分析。为了比较,我们还分析了磷脂。与先前的研究一致,我们观察到磷脂主要含有 C14:0 和 C19:0 环丙烷脂肪酸。相比之下,在脂蛋白中发现的酯键和酰胺键连接的脂肪酸几乎完全是 C16:0 和 C18:0。在其他细菌中,包括 和 ,也有报道称,膜磷脂和脂蛋白的酰基组成存在差异,这与本研究中报告的 情况一致。我们讨论了可能的机制。

重要性:
在全球范围内,胃癌是导致癌症相关死亡的第三大主要原因,而 定植于胃部是导致胃癌的一个重要危险因素。尽管细菌受到免疫反应的攻击,但仍能在胃中存活。TLR2 对脂蛋白的识别有助于对 的固有免疫反应。然而,脂蛋白在细菌持续存在中的作用尚不清楚。由于宿主对脂蛋白的反应取决于酰基链含量,因此确定脂蛋白的酰基组成是表征脂蛋白如何促进持续存在的重要步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11b8/11064636/2eda61d39a36/spectrum.00470-24.f001.jpg

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