铜绿假单胞菌延伸因子-Tu(EF-Tu)是一种免疫原性保护蛋白抗原。

Vaccine Pub Date : 2024-12-02 Epub Date: 2024-10-30 DOI:10.1016/j.vaccine.2024.126476
Dina A Moustafa, Emma Lou, Morgan E Schafer-Kestenman, Margalida Mateu-Borrás, Antonio Doménech-Sanchez, Sebastián Albertí, Joanna B Goldberg
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摘要

铜绿假单胞菌是一种革兰氏阴性机会性病原体,可感染免疫力低下的人,尤其是在医院环境中。这种细菌是免疫力低下、受伤和其他潜在生理机能障碍患者的重要病原体。在所有医院获得性肺炎中,铜绿假单胞菌的感染率高达 20%。它是引起院内感染的主要病因之一,也是合并感染 COVID-19 或在 COVID-19 感染后引起超级感染的最常见细菌之一。尽管抗菌治疗和医院护理有所改善,但仍有约 30% 的铜绿假单胞菌菌血症和肺炎病例是致命的。铜绿假单胞菌也是导致囊性纤维化患者发生危及生命的慢性肺部感染的主要原因。这种细菌天生具有抗生素耐药性,一旦感染就很难治疗,也没有疫苗可用。我们之前已经证明,铜绿假单胞菌表面暴露有伸长因子-Tu(EF-Tu),这是一种因其在蛋白质合成中的作用而最为人熟知的蛋白质。由于这种蛋白质表达量高,在进化过程中保持不变,而且是必不可少的,因此我们推测它将成为一个很好的疫苗靶标。在这项研究中,我们发现铜绿假单胞菌 EF-Tu 在人体内具有免疫原性,小鼠免疫重组铜绿假单胞菌 EF-Tu 后可产生免疫反应。此外,免疫后的小鼠在随后的铜绿假单胞菌肺炎中受到保护,将这种疫苗抗血清转移到天真小鼠身上可减少定植。总之,这些研究结果支持将 EF-Tu 作为一种新的铜绿假单胞菌候选疫苗。
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Pseudomonas aeruginosa elongation factor-Tu (EF-Tu) is an immunogenic protective protein antigen.

Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that infects immunocompromised individuals, especially in the hospital setting. This bacterium is an important pathogen in people with weakened immune systems, injuries, and other underlying physiologic dysfunctions. P. aeruginosa is responsible for up to 20 % of all hospital-acquired pneumonias. It is one of the major causes of nosocomial infections and has been noted to be one of the most common bacteria co-infecting patients with COVID-19 or causing super-infections following COVID-19 infections. Despite improvements in antimicrobial therapy and hospital care, P. aeruginosa bacteremia and pneumonia remain fatal in about 30 % of cases. P. aeruginosa is also the leading cause of chronic life-threatening lung infections in cystic fibrosis patients. This bacterium is naturally antibiotic resistant, and infections are notoriously difficult to treat once established, with no vaccine available. We have previously shown that elongation factor-Tu (EF-Tu), a protein best known for its role in protein synthesis, is surface exposed on P. aeruginosa. As this protein is highly expressed, evolutionally conserved, and essential, we hypothesized it would make a good vaccine target. In this study, we found that P. aeruginosa EF-Tu is immunogenic in people, and that mice can develop an immune response following immunization with recombinant P. aeruginosa EF-Tu. Furthermore, immunized mice were protected from subsequent P. aeruginosa pneumonia and transfer of this vaccine antisera to naïve mice resulted in decreased colonization. Altogether these findings support the consideration of EF-Tu as a new vaccine candidate against P. aeruginosa.

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