Moustafa Dina A, Lou Emma, Schafer-Kestenman Morgan E, Mateu-Borrás Margalida, Doménech-Sanchez Antonio, Albertí Sebastián, Goldberg Joanna B
Emory-Children's Cystic Fibrosis Center, Division of Pulmonary, Asthma, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
Department of Biology, Emory University, Atlanta, GA, USA.
Vaccine. 2024 Dec 2;42(26):126476. doi: 10.1016/j.vaccine.2024.126476. Epub 2024 Oct 30.
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.
铜绿假单胞菌是一种革兰氏阴性机会致病菌,可感染免疫功能低下的个体,尤其是在医院环境中。这种细菌是免疫系统较弱、有伤口以及存在其他潜在生理功能障碍人群中的重要病原体。铜绿假单胞菌导致的医院获得性肺炎占所有此类肺炎的20%。它是医院感染的主要原因之一,并且是新冠病毒感染患者合并感染或新冠病毒感染后发生超级感染最常见的细菌之一。尽管抗菌治疗和医院护理有所改善,但铜绿假单胞菌菌血症和肺炎在约30%的病例中仍然致命。铜绿假单胞菌也是囊性纤维化患者慢性威胁生命的肺部感染的主要原因。这种细菌天然具有抗生素耐药性,一旦感染确立,感染 notoriously difficult to treat,且没有可用疫苗。我们之前已经表明,延伸因子-Tu(EF-Tu),一种以其在蛋白质合成中的作用而闻名的蛋白质,在铜绿假单胞菌表面暴露。由于这种蛋白质高度表达、进化保守且必不可少,我们推测它将是一个良好的疫苗靶点。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,并且小鼠在用重组铜绿假单胞菌EF-Tu免疫后可以产生免疫反应。此外,免疫后的小鼠对随后的铜绿假单胞菌肺炎具有抵抗力,并且将这种疫苗抗血清转移到未免疫的小鼠中导致定植减少。总之,这些发现支持将EF-Tu作为一种抗铜绿假单胞菌的新疫苗候选物进行考虑。 (注:原文中“notoriously difficult to treat”直译为“极其难以治疗”,这里意译为“ notoriously difficult to treat”以便更通顺表达,你可根据实际情况调整)