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多克隆抗全细胞 IgY 被动免疫疗法可预防铜绿假单胞菌引起的小鼠急性肺炎和烧伤创面感染。

Polyclonal anti-whole cell IgY passive immunotherapy shields against P. aeruginosa-induced acute pneumonia and burn wound infections in murine models.

机构信息

Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran-Qom Express Way, Tehran, 3319118651, Iran.

出版信息

Sci Rep. 2024 Jan 3;14(1):405. doi: 10.1038/s41598-023-50859-x.

Abstract

Pseudomonas aeruginosa (PA) is a multidrug-resistant (MDR) opportunistic pathogen causing severe hospital-, and community-acquired infections worldwide. Thus, the development of effective immunotherapy-based treatments is essential to combat the MDR-PA infections. In the current study, we evaluated the protective efficacy of polyclonal avian antibodies raised against inactivated whole cells of the PAO1 strain in murine models of acute pneumonia and burn wound. The efficacy of generated antibodies was evaluated against different PA strains through several in vitro, ex vivo and in vivo experiments. The results showed that the anti-PAO1-IgY effectively reduced the motility, biofilm formation and cell internalization ability, and enhanced the opsonophagocytic killing of PA strains through the formation of immobilized bacteria and induction of increased cell surface hydrophobicity. Furthermore, immunotherapy with anti-PAO1-IgY completely protected mice against all PA strains in both acute pneumonia and burn wound murine models. It was found to reduce the bacterial loads in infected burned mice through interfering with virulence factors that play vital roles in the early stages of PA infection, such as colonization and cell internalization. The immunotherapy with anti-PAO1-IgYs could be instrumental in developing effective therapies aimed at reducing the morbidity and mortality associated with PA infections.

摘要

铜绿假单胞菌(PA)是一种多药耐药(MDR)的机会性病原体,可导致全球严重的医院和社区获得性感染。因此,开发基于有效的免疫疗法的治疗方法对于对抗 MDR-PA 感染至关重要。在本研究中,我们评估了针对 PAO1 菌株灭活全细胞产生的多克隆禽抗体在急性肺炎和烧伤创面小鼠模型中的保护效力。通过多项体外、离体和体内实验评估了产生的抗体对不同 PA 株的疗效。结果表明,抗 PAO1-IgY 可有效降低 PA 株的运动性、生物膜形成和细胞内化能力,并通过固定细菌的形成和诱导增加细胞表面疏水性增强对 PA 株的调理吞噬杀伤作用。此外,抗 PAO1-IgY 的免疫疗法可完全保护小鼠免受急性肺炎和烧伤创面小鼠模型中所有 PA 株的感染。研究发现,它通过干扰在 PA 感染早期阶段发挥重要作用的毒力因子(如定植和细胞内化),减少感染烧伤小鼠的细菌负荷。抗 PAO1-IgY 的免疫疗法可能有助于开发针对降低与 PA 感染相关的发病率和死亡率的有效疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d121/10764880/17aa88ed3fd3/41598_2023_50859_Fig1_HTML.jpg

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