A pneumococcal pilus influences virulence and host inflammatory responses
A pneumococcal pilus influences virulence and host inflammatory responses
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DOI：
10.1073/pnas.0511017103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Henriques-Normark, B
中科院分区：
文献类型：
--
作者：
Barocchi, MA;Rie, J;Henriques-Normark, B
肺炎链球菌（肺炎球菌）是世界范围内发病率和死亡率的主要原因。侵袭性肺炎球菌疾病的初始事件是包裹性肺炎球菌附着在上呼吸道上皮细胞上。这项工作提供了证据，证明细菌最初的粘附和随后引起侵袭性疾病的能力是由菌毛增强的，菌毛是一种能够延伸到多糖胶囊之外的长细胞器，以前未知的存在于肺炎球菌中。这些黏附的毛状附属物由肺炎球菌rlrA胰岛编码，存在于一些但不是全部的临床分离株中。将rlrA胰岛引入包封的rlrA阴性分离物中，允许毛表达，增强对肺上皮细胞的粘附，并在小鼠混合鼻内挑战时提供竞争优势。此外，表达毛毛的rlrA胰岛阳性临床分离物比非毛毛缺失突变体更具毒性，并且在小鼠定植、肺炎和菌血症模型中优于突变体。此外，与非毛状肺炎球菌衍生物相比，毛状肺炎球菌在全身性感染期间引起了更高的TNF反应，这表明肺炎球菌毛不仅有助于粘附和毒力，而且还刺激宿主的炎症反应。
Streptococcus pneumonrae (pneumococcus) is a major cause of morbidity and mortality world-wide. The initial event in invasive pneumococcal disease is the attachment of encapsulated pneumococci to epithelial cells in the upper respiratory tract. This work provides evidence that initial bacterial adhesion and subsequent ability to cause invasive disease is enhanced by pili, long organelles able to extend beyond the polysaccharide capsule, previously unknown to exist in pneumococci. These adhesive pili-like appendages are encoded by the pneumococcal rlrA islet, present in some, but not all, clinical isolates. Introduction of the rlrA islet into an encapsulated rlrA-negative isolate allowed pilus expression, enhanced adherence to lung epithelial cells, and provided a competitive advantage upon mixed intranasal challenge of mice. Furthermore, a pilus-expressing rlrA islet-positive clinical isolate was more virulent than a nonpiliated deletion mutant, and it out-competed the mutant in murine models of colonization, pneumonia, and bacteremia. Additionally, piliated pneumococci evoked a higher TNF response during systemic infection, compared with nonpiliated derivatives, suggesting that pneumococcal pili not only contribute to adherence and virulence but also stimulate the host inflammatory response.