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细胞毒素RtxA可诱导口腔上皮细胞产生先天性免疫反应。

cytotoxin RtxA induces an innate immune response in oral epithelial cells.

作者信息

Ruzickova Eliska, Zhuk Karyna, Navarrete Kevin Munoz, Osickova Adriana, Osicka Radim

机构信息

Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.

Faculty of Science, Charles University, Prague, Czech Republic.

出版信息

Curr Res Microb Sci. 2025 Apr 17;8:100393. doi: 10.1016/j.crmicr.2025.100393. eCollection 2025.

DOI:10.1016/j.crmicr.2025.100393
PMID:40666162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12261957/
Abstract

The genus comprises four common species: the commensals and , the emerging paediatric pathogen and the novel species . Improved diagnostic methods have led to the recognition of as a major cause of septic arthritis in young children. The key virulence factor responsible for the pathogenesis of is its cytotoxin RtxA, which is thought to facilitate host invasion. After binding to target cells, RtxA inserts into the host cell membrane and forms ion-conducting membrane pores that disrupt normal cell physiology and ultimately lead to cell death. In this study, we analysed the pro-inflammatory response of oral epithelial cells to a clinical isolate of , its isogenic RtxA-deficient mutant and the commensals and , which do not produce RtxA. The results show that infection of cells with , but not with the RtxA-deficient mutant and the commensal species, leads to increased expression and secretion of certain pro-inflammatory cytokines and chemokines. Furthermore, the RtxA-producing , but not the RtxA-deficient mutant, upregulated the expression of and genes encoding antimicrobial peptides. These findings demonstrate that the RtxA toxin induces an innate immune response in oral epithelial cells.

摘要

该属包括四个常见物种

共生菌 和 、新兴的儿科病原体 以及新物种 。改进的诊断方法已使人们认识到 是幼儿化脓性关节炎的主要病因。导致 发病机制的关键毒力因子是其细胞毒素RtxA,据认为它有助于宿主入侵。与靶细胞结合后,RtxA插入宿主细胞膜并形成离子传导膜孔,破坏正常细胞生理功能并最终导致细胞死亡。在本研究中,我们分析了口腔上皮细胞对 的临床分离株、其同基因RtxA缺陷突变体以及不产生RtxA的共生菌 和 的促炎反应。结果表明,用 感染细胞,但不用RtxA缺陷突变体和共生菌感染细胞,会导致某些促炎细胞因子和趋化因子的表达和分泌增加。此外,产生RtxA的 ,而不是RtxA缺陷突变体,上调了编码抗菌肽的 和 基因的表达。这些发现表明,RtxA毒素在口腔上皮细胞中诱导先天免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/8f40fc2a93a7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/4e734a4c8bee/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/b325888845bb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/179ed56b8fa5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/ace0d81d1298/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/7c2cb177670b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/fdea94e53b84/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/be536ede8e11/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/8f40fc2a93a7/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/4e734a4c8bee/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/b325888845bb/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/179ed56b8fa5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/ace0d81d1298/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/7c2cb177670b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/fdea94e53b84/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/be536ede8e11/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7acc/12261957/8f40fc2a93a7/gr7.jpg

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本文引用的文献

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Structural and functional significance of two conserved lysine residues in acylated sites of Kingella kingae RtxA cytotoxin.
Biochimie. 2025 May;232:105-116. doi: 10.1016/j.biochi.2024.12.016. Epub 2024 Dec 31.
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Two pairs of back-to-back α-helices of Kingella kingae RtxA toxin are crucial for the formation of a membrane pore.
Int J Biol Macromol. 2024 Dec;283(Pt 1):137604. doi: 10.1016/j.ijbiomac.2024.137604. Epub 2024 Nov 13.
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Acquisition, co-option, and duplication of the rtx toxin system and the emergence of virulence in Kingella.金氏菌中 rtx 毒素系统的获得、共进化和复制,以及毒力的出现。
Nat Commun. 2023 Jul 17;14(1):4281. doi: 10.1038/s41467-023-39939-8.
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Kingella kingae RtxA toxin interacts with sialylated gangliosides.溶血隐秘杆菌RtxA毒素与唾液酸化神经节苷脂相互作用。
Microb Pathog. 2023 Aug;181:106200. doi: 10.1016/j.micpath.2023.106200. Epub 2023 Jun 13.
5
Whole-Genome Sequencing Reveals Differences among Kingella kingae Strains from Carriers and Patients with Invasive Infections.全基因组测序揭示了侵袭性感染携带者和患者的金氏金菌菌株之间的差异。
Microbiol Spectr. 2023 Jun 15;11(3):e0389522. doi: 10.1128/spectrum.03895-22. Epub 2023 May 17.
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Kingella pumchi sp. nov., an organism isolated from human vertebral puncture tissue.普姆奇金氏菌新种,一种从人体脊椎穿刺组织中分离出的微生物。
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