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因子 H 相关蛋白 3 在血流感染中的作用。

Role of factor H-related protein 3 in bloodstream infections.

机构信息

Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.

Center for Biological Research-Margarita Salas and Centro de Investigación Biomédica En Red (CIBER) de Enfermedades Raras, Madrid, Spain.

出版信息

Front Immunol. 2024 Sep 4;15:1449003. doi: 10.3389/fimmu.2024.1449003. eCollection 2024.

DOI:10.3389/fimmu.2024.1449003
PMID:39295874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408224/
Abstract

Pseudomonas aeruginosa is a leading cause of nosocomial bloodstream infections. The outcome of these infections depends on the virulence of the microorganism as well as host-related conditions and factors. The complement system plays a crucial role in defense against bloodstream infections. counteracts complement attack by recruiting Factor H (FH) that inhibits complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere this bacterial evasion mechanism. In this study, we demonstrate that FHR-3 competes with purified FH for binding to and identify EF-Tu as a common bacterial target for both complement regulator factors. Importantly, elevated levels of FHR-3 in human serum promote complement activation, leading to increased opsonization and killing of . Conversely, physiological concentrations of FHR-3 have no significant effect. Our findings suggest that FHR-3 may serve as a protective host factor against infections.

摘要

铜绿假单胞菌是医院获得性血流感染的主要致病菌。这些感染的结果取决于微生物的毒力以及宿主相关的条件和因素。补体系统在抵御血流感染中起着至关重要的作用。通过招募因子 H (FH)来中和补体攻击，从而抑制细菌表面的补体放大。因子 H 相关蛋白 (FHRs) 是一组与 FH 具有进化关系的血浆蛋白，据推测它们可以干扰这种细菌逃避机制。在这项研究中，我们证明 FHR-3 与 竞争结合，并确定 EF-Tu 是这两种补体调节因子的共同细菌靶标。重要的是，人血清中 FHR-3 水平的升高可促进补体激活，导致 被更多地调理和杀伤。相反，生理浓度的 FHR-3 没有显著影响。我们的研究结果表明，FHR-3 可能作为一种保护性宿主因子，对抗 感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/42caf691daa9/fimmu-15-1449003-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/649b375edb80/fimmu-15-1449003-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/59a3c91e8218/fimmu-15-1449003-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/b456edfd6fa0/fimmu-15-1449003-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/eb3e25186837/fimmu-15-1449003-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/f55841bde622/fimmu-15-1449003-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/42caf691daa9/fimmu-15-1449003-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/649b375edb80/fimmu-15-1449003-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/59a3c91e8218/fimmu-15-1449003-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/b456edfd6fa0/fimmu-15-1449003-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/eb3e25186837/fimmu-15-1449003-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/f55841bde622/fimmu-15-1449003-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d21f/11408224/42caf691daa9/fimmu-15-1449003-g006.jpg

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本文引用的文献

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Front Cell Infect Microbiol. 2024 Mar 6;14:1328185. doi: 10.3389/fcimb.2024.1328185. eCollection 2024.
2
The Factor H protein family: The switchers of the complement alternative pathway.补体旁路途径的开关：因子 H 蛋白家族。
Immunol Rev. 2023 Jan;313(1):25-45. doi: 10.1111/imr.13166. Epub 2022 Nov 16.
3
Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation.
补体因子 H 相关蛋白 FHR1 和 FHR5 与细胞外基质配体相互作用，降低因子 H 调节活性并增强补体激活。
Front Immunol. 2022 Mar 22;13:845953. doi: 10.3389/fimmu.2022.845953. eCollection 2022.
4
Molecular Analysis of the Contribution of Alkaline Protease A and Elastase B to the Virulence of Bloodstream Infections.碱性蛋白酶 A 和弹性蛋白酶 B 对血流感染毒力的分子分析。
Front Cell Infect Microbiol. 2022 Jan 12;11:816356. doi: 10.3389/fcimb.2021.816356. eCollection 2021.
5
Bacterial behavior in human blood reveals complement evaders with some persister-like features.在人血中，细菌的行为表现揭示了一些具有类似持久性特征的补体逃避者。
PLoS Pathog. 2020 Dec 16;16(12):e1008893. doi: 10.1371/journal.ppat.1008893. eCollection 2020 Dec.
6
High Complement Factor H-Related (FHR)-3 Levels Are Associated With the Atypical Hemolytic-Uremic Syndrome-Risk Allele .高补体因子 H 相关（FHR）-3 水平与非典型溶血尿毒综合征风险等位基因相关。
Front Immunol. 2018 Apr 24;9:848. doi: 10.3389/fimmu.2018.00848. eCollection 2018.
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Sensing Mg contributes to the resistance of Pseudomonas aeruginosa to complement-mediated opsonophagocytosis.感受镁元素有助于铜绿假单胞菌抵抗补体介导的调理吞噬作用。
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