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非侵袭性细菌病原体鼠柠檬酸杆菌的肠道微生物群非依赖性毒力。

The gut microbiota-independent virulence of noninvasive bacterial pathogen Citrobacter rodentium.

作者信息

Liu Yue, Xu Dongqing, Guo Songwei, Wang Shuyu, Ding Hua, Siu Catherine, Wan Fengyi

机构信息

Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.

出版信息

PLoS Pathog. 2024 Dec 4;20(12):e1012758. doi: 10.1371/journal.ppat.1012758. eCollection 2024 Dec.

DOI:10.1371/journal.ppat.1012758
PMID:39630719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11649119/
Abstract

Attaching and effacing (A/E) bacterial pathogens consist of human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli and their murine equivalent Citrobacter rodentium (CR). Emerging evidence suggests that the complex pathogen-microbiota-host interactions are critical in conferring A/E pathogen infection-induced severe symptoms and lethality in immunocompromised hosts; however, the precise underlying mechanisms remain enigmatic. Here we report that CR infection causes severe colitis and mortality in interleukin 22 knockout (Il22-/-) and Rag1 knockout (Rag1-/-) mice under germ-free (GF) conditions. In a gut microbiota-independent manner, CR colonizes in GF Il22-/- and Rag1-/- animals, triggers colonic epithelial tissue damage and systemic dissemination of CR, and results in lethal infections. Pretreatment with cefoxitin, a broad-spectrum antibiotic, exacerbates CR-induced colitis and lethality in specific-pathogen-free (SPF) Il22-/- and Rag1-/- mice. Together our results reveal that CR possesses a gut microbiota-independent virulence, which is better illustrated during infections in immunocompromised hosts associated with severe outcomes.

摘要

黏附性侵袭性（A/E）细菌病原体包括人类病原体肠致病性大肠杆菌、肠出血性大肠杆菌及其小鼠等效物鼠柠檬酸杆菌（CR）。新出现的证据表明，复杂的病原体-微生物群-宿主相互作用对于免疫受损宿主中A/E病原体感染诱导的严重症状和致死率至关重要；然而，确切的潜在机制仍然不明。在此我们报告，在无菌（GF）条件下，CR感染在白细胞介素22基因敲除（Il22-/-）和Rag1基因敲除（Rag1-/-）小鼠中导致严重结肠炎和死亡。以一种不依赖肠道微生物群的方式，CR在GF Il22-/-和Rag1-/-动物中定殖，引发结肠上皮组织损伤和CR的全身播散，并导致致命感染。用广谱抗生素头孢西丁预处理会加重无特定病原体（SPF）Il22-/-和Rag1-/-小鼠中CR诱导的结肠炎和致死率。我们的结果共同揭示，CR具有一种不依赖肠道微生物群的毒力，这在与严重后果相关的免疫受损宿主感染期间得到了更好的体现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/f6905d5c5e17/ppat.1012758.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/02087da3fecd/ppat.1012758.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/b365c7c94dec/ppat.1012758.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/3a4154d39ee2/ppat.1012758.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/f6905d5c5e17/ppat.1012758.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/02087da3fecd/ppat.1012758.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/b365c7c94dec/ppat.1012758.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/3a4154d39ee2/ppat.1012758.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d107/11649119/f6905d5c5e17/ppat.1012758.g004.jpg

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本文引用的文献

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Complement in breast milk modifies offspring gut microbiota to promote infant health.母乳中的补体调节子代肠道微生物群，促进婴儿健康。
Cell. 2024 Feb 1;187(3):750-763.e20. doi: 10.1016/j.cell.2023.12.019. Epub 2024 Jan 18.
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Quantitative dose-response analysis untangles host bottlenecks to enteric infection.定量剂量反应分析解开了宿主对肠道感染的瓶颈。
Nat Commun. 2023 Jan 28;14(1):456. doi: 10.1038/s41467-023-36162-3.
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Bacterial Genotoxin Accelerates Transient Infection-Driven Murine Colon Tumorigenesis.细菌遗传毒素加速瞬时感染诱导的小鼠结肠肿瘤发生。
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Citrobacter rodentium-host-microbiota interactions: immunity, bioenergetics and metabolism.柠檬酸杆菌-宿主微生物群相互作用：免疫、生物能量学和代谢。
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EspF is crucial for Citrobacter rodentium-induced tight junction disruption and lethality in immunocompromised animals.EspF 对于枸橼酸杆菌引起的免疫功能低下动物的紧密连接破坏和致死至关重要。
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