JCI:脑膜炎的新疫苗能有效对抗肺炎链球菌株

2012-05-29 Beyond 生物谷

细菌性脑膜炎是一类严重感染性疾病,病死率和后遗症发生率高。在充分考虑病原学特点和抗菌药物、药理特性的基础上进行及时、有效的抗菌治疗,是提高治愈率、降低病死率和减少后遗症的保证。 最近,澳大利亚阿德莱德大学的研究人员试图找出新疫苗来抵抗肺炎链球菌,肺炎链球菌是引发细菌性脑膜炎最常见的致病原因。 利用小鼠动物模型系统,研究人员研究了能感染小鼠的两个不同的肺炎链球菌株。他们发现一种称为磷酸甘油氧化

细菌性脑膜炎是一类严重感染性疾病,病死率和后遗症发生率高。在充分考虑病原学特点和抗菌药物、药理特性的基础上进行及时、有效的抗菌治疗,是提高治愈率、降低病死率和减少后遗症的保证。

最近,澳大利亚阿德莱德大学的研究人员试图找出新疫苗来抵抗肺炎链球菌,肺炎链球菌是引发细菌性脑膜炎最常见的致病原因。

利用小鼠动物模型系统,研究人员研究了能感染小鼠的两个不同的肺炎链球菌株。他们发现一种称为磷酸甘油氧化酶的蛋白质是细菌从血液进入小鼠大脑中的关键。他们还证实抗甘油氧化酶的疫苗能保护小鼠免受肺炎球菌疾病的入侵。其结果不仅揭示了对抗肺炎链球菌的免疫新策略,而且为从其他导致脑膜炎病原体中发现致病基因提供了新方法。

doi:10.1172/JCI45850
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Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice

Layla K. Mahdi1, Hui Wang1, Mark B. Van der Hoek2, James C. Paton1 and Abiodun D. Ogunniyi1

Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H2O2. A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens.

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