Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae
Role of pneumococcal surface protein C in nasopharyngeal carriage and pneumonia and its ability to elicit protection against carriage of Streptococcus pneumoniae
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DOI：
10.1128/iai.70.5.2526-2534.2002
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发表时间：
2002-05-01
影响因子：
3.1
通讯作者：
Briles, DE
中科院分区：
文献类型：
--
作者：
Balachandran, P;Brooks-Walter, A;Briles, DE
先前的研究表明，PspC 对于鼻咽内的粘附和定植非常重要。在本研究中，我们进行了突变研究，以进一步确定 PspC 在肺炎球菌发病机制中的作用。 pspC 和/或 pspA 在血清型 2 肺炎链球菌菌株和血清型 19 肺炎链球菌菌株中被插入灭活。在小鼠定植模型中，pspC 突变的肺炎球菌菌株的定植能力显着减弱。在小鼠肺炎模型中，pspC 突变的菌株无法在肺部感染或繁殖。使用逆转录酶 PCR，我们能够证明当细菌在鼻腔和肺部生长时，pspC 在体内活跃转录。在菌血症模型中，仅 pspC 突变的菌株表现得与野生型相似，但 pspC 和 pspA 的缺失导致细菌的加速清除。使用 PspC 和霍乱毒素 B 亚基作为佐剂进行鼻内免疫，可防止鼻内攻击。还获得的证据表明，自发获得 PspC 表达的回复体可以在鼻组织中繁殖和定植。后一个发现强烈表明肺炎球菌在鼻咽中代谢和生长活跃。
Previous studies suggested that PspC is important in adherence and colonization within the nasopharynx. In this study, we conducted mutational studies to further identify the role PspC plays in the pathogenesis of pneumococci. pspC and/or pspA was insertionally inactivated in a serotype 2 Streptococcus pneumoniae strain and in a serotype 19 S. pneumoniae strain. In the mouse colonization model, pneumococcal strains with mutations in pspC were significantly attenuated in their abilities to colonize. In a mouse pneumonia model, strains with mutations in pspC were unable to infect or multiply within the lung. Using reverse transcriptase PCR we were able to demonstrate that pspC is actively transcribed in vivo, when the bacteria are growing in the nasal cavity and in the lungs. In the bacteremia model, a strain mutated for pspC alone behaved like the wild type, but the absence of both pspC and pspA caused accelerated clearance of the bacteria. Intranasal immunization with PspC with cholera toxin subunit B as an adjuvant protected against intranasal challenge. Evidence was also obtained that revertants that spontaneously acquired PspC expression could multiply and colonize the nasal tissue. This latter finding strongly indicates that pneumococci are actively metabolizing and growing while in the nasopharynx.