Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes.
Meningitis-associated pneumococcal serotype 8, ST 53, strain is hypervirulent in a rat model and has non-haemolytic pneumolysin which can be attenuated by liposomes.
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DOI：
10.3389/fcimb.2022.1106063
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发表时间：
2022
影响因子：
5.7
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中科院分区：
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肺炎链球菌可引起危及生命的侵袭性肺炎球菌疾病 (IPD)，包括脑膜炎。肺炎球菌根据荚膜多糖的差异分为血清型，血清型和肺炎球菌溶血素毒素均与疾病严重程度相关。在一些国家，血清型 8（ST 53）菌株在 IPD 中的患病率正在增加。在这里，我们在脑膜炎大鼠模型中测试了这种分离株的毒力，并与血清型 15B 和血清型 14 分离株进行了比较。这三者均于 2019 年从南非的脑膜炎患者中分离出来，其中血清型 8 是目前 IPD 最常见的血清型。只有血清型 8 分离株具有高毒力，可导致脑损伤和高死亡率。在大鼠模型中以及从小鼠大脑中分离出的原代混合神经胶质细胞中，它比血清型 15B 或 14 菌株诱导了更强的炎症细胞因子反应。它具有三种菌株中最厚的荚膜，并产生非溶血性肺炎球菌溶血素。肺炎球菌溶血素隔离脂质体在体外降低了神经炎症细胞因子反应，表明脂质体有潜力成为有效的辅助治疗，甚至对于具有非溶血性肺炎球菌溶血素的高毒力肺炎球菌菌株也是如此。
Streptococcus pneumoniae bacteria cause life-threatening invasive pneumococcal disease (IPD), including meningitis. Pneumococci are classified into serotypes, determined by differences in capsular polysaccharide and both serotype and pneumolysin toxin are associated with disease severity. Strains of serotype 8, ST 53, are increasing in prevalence in IPD in several countries. Here we tested the virulence of such an isolate in a rat model of meningitis in comparison with a serotype 15B and a serotype 14 isolate. All three were isolated from meningitis patients in South Africa in 2019, where serotype 8 is currently the most common serotype in IPD. Only the serotype 8 isolate was hypervirulent causing brain injury and a high mortality rate. It induced a greater inflammatory cytokine response than either the serotype 15B or 14 strain in the rat model and from primary mixed-glia cells isolated from mouse brains. It had the thickest capsule of the three strains and produced non-haemolytic pneumolysin. Pneumolysin-sequestering liposomes reduced the neuroinflammatory cytokine response in vitro indicating that liposomes have the potential to be an effective adjuvant therapy even for hypervirulent pneumococcal strains with non-haemolytic pneumolysin.