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巨噬细胞感染后潜在致病性相关蛋白的变化。 (你提供的原文似乎不完整,“of”后面缺少具体内容)

Changes in potential pathogenicity-associated proteins of upon infection of macrophage cells.

作者信息

Voronina A K, Efimov B A, Malakhova M V, Shnaider P V, Ivanova O M, Bogomiakova M, Shender V O, Lagarkova M A, Arapidi G P

机构信息

Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, Moscow, Russia.

Federal State Autonomous Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University" of the Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Front Microbiol. 2025 Aug 25;16:1640829. doi: 10.3389/fmicb.2025.1640829. eCollection 2025.

Abstract

INTRODUCTION

is a spiral-shaped Gram-negative, enterohepatic bacterium classified as a conditional pathogen (pathogenicity group 2). It is known to cause bacteremia and a variety of other diseases in humans. In particular, has been shown to impair intracellular cholesterol metabolism when interacting with macrophages, leading to foam cell formation. M1-macrophages transformed into the foam cell phenotype contribute to atherosclerotic plaques, suggesting a potential link between infection and atherosclerosis development.

METHODS

To uncover protein factors involved in pathogenesis, we performed a detailed mass spectrometric analysis of the proteome of strain BAA-847. This study represents the first comprehensive analysis of the bacterium's proteome under standard culture conditions and after infection of M1-type macrophage cells.

RESULTS

We identified 1,575 proteins in the proteome, 109 of which were differentially upregulated after macrophage infection. Functional analysis revealed roles for these proteins in immune evasion, intracellular survival, and potential pathogenicity. Beyond known virulence factors (HcaA, Cdt, AhpC), we identified poorly characterized proteins with toxic or immunomodulatory functions. Notably, some upregulated proteins enable cholesterol utilization as a carbon source, while others may participate in a toxin injection mechanism disrupting host cell metabolism-potentially linked to foam cell formation.

CONCLUSION

Our findings provide new insights into pathogenicity, highlighting previously unexplored virulence mechanisms. The identified proteins could serve as targets for further research into -associated diseases, including atherosclerosis.

摘要

引言

是一种螺旋状革兰氏阴性肠肝菌,被归类为条件致病菌(致病组2)。已知它会在人类中引起菌血症和多种其他疾病。特别是,已证明与巨噬细胞相互作用时会损害细胞内胆固醇代谢,导致泡沫细胞形成。转化为泡沫细胞表型的M1巨噬细胞会促成动脉粥样硬化斑块,这表明感染与动脉粥样硬化发展之间可能存在联系。

方法

为了揭示参与发病机制的蛋白质因子,我们对菌株BAA - 847的蛋白质组进行了详细的质谱分析。这项研究代表了在标准培养条件下以及感染M1型巨噬细胞后对该细菌蛋白质组的首次全面分析。

结果

我们在蛋白质组中鉴定出1575种蛋白质,其中109种在巨噬细胞感染后差异上调。功能分析揭示了这些蛋白质在免疫逃避、细胞内存活和潜在致病性方面的作用。除了已知的毒力因子(HcaA、Cdt、AhpC)外,我们还鉴定出了具有毒性或免疫调节功能但特征不明的蛋白质。值得注意的是,一些上调的蛋白质能够将胆固醇用作碳源,而其他蛋白质可能参与破坏宿主细胞代谢的毒素注射机制——这可能与泡沫细胞形成有关。

结论

我们的发现为发病机制提供了新的见解,突出了以前未探索的毒力机制。所鉴定的蛋白质可作为进一步研究包括动脉粥样硬化在内的相关疾病的靶点。

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