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从鼠粪便中分离的噬菌体可减轻铜绿假单胞菌引起的肺炎小鼠的病情。

Bacteriophages isolated from mouse feces attenuates pneumonia mice caused by Pseudomonas aeruginosa.

机构信息

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Microbiology, Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

PLoS One. 2024 Jul 16;19(7):e0307079. doi: 10.1371/journal.pone.0307079. eCollection 2024.


DOI:10.1371/journal.pone.0307079
PMID:39012882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251617/
Abstract

BACKGROUND: Most of the current bacteriophages (phages) are mostly isolated from environments. However, phages isolated from feces might be more specific to the bacteria that are harmful to the host. Meanwhile, some phages from the environment might affect non-pathogenic bacteria for the host. METHODS: Here, bacteriophages isolated from mouse feces were intratracheally (IT) or intravenously (IV) administered in pneumonia mice caused by Pseudomonas aeruginosa at 2 hours post-intratracheal bacterial administration. As such, the mice with phage treatment, using either IT or IV administration, demonstrated less severe pneumonia as indicated by mortality, serum cytokines, bacteremia, bacterial abundance in bronchoalveolar lavage fluid (BALF), and neutrophil extracellular traps (NETs) in lung tissue (immunofluorescence of neutrophil elastase and myeloperoxidase). RESULTS: Interestingly, the abundance of phages in BALF from the IT and IV injections was similar, supporting a flexible route of phage administration. With the incubation of bacteria with neutrophils, the presence of bacteriophages significantly improved bactericidal activity, but not NETs formation, with the elevated supernatant IL-6 and TNF-α, but not IL-1β. In conclusion, our findings suggest that bacteriophages against Pseudomonas aeruginosa can be discovered from feces of the host. CONCLUSIONS: The phages attenuate pneumonia partly through an enhanced neutrophil bactericidal activity, but not via inducing NETs formation. The isolation of phages from the infected hosts themselves might be practically useful for future treatment. More studies are warranted.

摘要

背景:目前大多数噬菌体(phages)主要从环境中分离得到。然而,从粪便中分离得到的噬菌体可能对宿主有害的细菌更具特异性。同时,环境中的一些噬菌体可能会影响宿主的非致病性细菌。

方法:在这里,从小鼠粪便中分离得到的噬菌体在铜绿假单胞菌经气管内(IT)或静脉内(IV)给药 2 小时后,用于肺炎小鼠。因此,用 IT 或 IV 给药进行噬菌体治疗的小鼠,其死亡率、血清细胞因子、菌血症、支气管肺泡灌洗液(BALF)中的细菌丰度和肺组织中的中性粒细胞胞外陷阱(NETs)(中性粒细胞弹性蛋白酶和髓过氧化物酶的免疫荧光)表明肺炎程度较轻。

结果:有趣的是,IT 和 IV 注射后 BALF 中噬菌体的丰度相似,支持噬菌体给药的灵活途径。随着细菌与中性粒细胞孵育,噬菌体的存在显著提高了杀菌活性,但不增加 NETs 的形成,同时上清液中 IL-6 和 TNF-α水平升高,但 IL-1β 水平没有升高。总之,我们的研究结果表明,针对铜绿假单胞菌的噬菌体可以从宿主的粪便中发现。

结论:噬菌体部分通过增强中性粒细胞的杀菌活性来减轻肺炎,而不是通过诱导 NETs 的形成。从感染宿主自身分离噬菌体可能对未来的治疗具有实际意义。需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/5b94cad827d6/pone.0307079.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/9018d3deaee9/pone.0307079.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/bfbfbc6c2d74/pone.0307079.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/5cd6f1cb73d9/pone.0307079.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/4039796f1d02/pone.0307079.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/611301d89c48/pone.0307079.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/5b94cad827d6/pone.0307079.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/9018d3deaee9/pone.0307079.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/bfbfbc6c2d74/pone.0307079.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/5cd6f1cb73d9/pone.0307079.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/4039796f1d02/pone.0307079.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/611301d89c48/pone.0307079.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38f9/11251617/5b94cad827d6/pone.0307079.g006.jpg

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[5]
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[6]
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本文引用的文献

[1]
Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University.

Sci Rep. 2024-2-1

[2]
Human Neutrophil Response to Bacteriophage PAK_P1, a Therapeutic Candidate.

Viruses. 2023-8-12

[3]
Cyclic GMP-AMP Synthase (cGAS) Deletion Reduces Severity in Bilateral Nephrectomy Mice through Changes in Neutrophil Extracellular Traps and Mitochondrial Respiration.

Biomedicines. 2023-4-18

[4]
High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions.

Biomedicines. 2022-12-25

[5]
Bacteriophage: A new therapeutic player to combat neutrophilic inflammation in chronic airway diseases.

Front Med (Lausanne). 2022-12-14

[6]
Epidemiology of pneumonia in hospitalized adults ≥18 years old in four districts of Ulaanbaatar, Mongolia, 2015-2019.

Lancet Reg Health West Pac. 2022-9-10

[7]
Bacteriophage Effectively Rescues Pneumonia Caused by Prevalent Multidrug-Resistant in the Early Stage.

Microbiol Spectr. 2022-10-26

[8]
Critical roles of sepsis-reshaped fecal virota in attenuating sepsis severity.

Front Immunol. 2022

[9]
Chlorhexidine Promotes Expression in That Enhances Cell Aggregation with Preserved Pathogenicity Demonstrates an Adaptation against Antiseptic.

Int J Mol Sci. 2022-7-27

[10]
Evolutionary Dynamics between Phages and Bacteria as a Possible Approach for Designing Effective Phage Therapies against Antibiotic-Resistant Bacteria.

Antibiotics (Basel). 2022-7-7

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