Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Department of Molecular Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Infect Immun. 2014 Sep;82(9):3790-801. doi: 10.1128/IAI.01840-14. Epub 2014 Jun 23.
The polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule. In this study, the S. mitis type strain switched capsule by acquisition of the serotype 4 capsule locus of S. pneumoniae TIGR4, following induction of competence for natural transformation. Comparison of the wild type with the capsule-switching mutant and with a capsule deletion mutant showed that the capsule protected S. mitis against phagocytosis by RAW 264.7 macrophages. This effect was enhanced in the S. mitis strain expressing the S. pneumoniae capsule, which showed, in addition, increased resistance against early clearance in a mouse model of lung infection. Expression of both capsules also favored survival in human blood, and the effect was again more pronounced for the capsule-switching mutant. S. mitis survival in horse blood or in a mouse model of bacteremia was not significantly different between the wild type and the mutant strains. In all models, S. pneumoniae TIGR4 showed higher rates of survival than the S. mitis type strain or the capsule-switching mutant, except in the lung model, in which significant differences between S. pneumoniae TIGR4 and the capsule-switching mutant were not observed. Thus, we identified conditions that showed a protective function for the capsule in S. mitis. Under such conditions, S. mitis resistance to clearance could be enhanced by capsule switching to serotype 4, but it was enhanced to levels lower than those for the virulent strain S. pneumoniae TIGR4.
肺炎链球菌荚膜对于其毒力至关重要。最近，研究发现一种人类共生菌——口腔链球菌，也具有荚膜。在本研究中，口腔链球菌通过获取肺炎链球菌 TIGR4 的 4 型荚膜基因座，在自然转化感受态诱导后发生荚膜转换。与野生型相比，荚膜转换突变株和荚膜缺失突变株均表明荚膜可以保护口腔链球菌免受 RAW264.7 巨噬细胞的吞噬。这种作用在表达肺炎链球菌荚膜的口腔链球菌菌株中得到增强，并且在肺炎感染的小鼠模型中，该菌株还表现出早期清除的抗性增加。两种荚膜的表达均有利于在人血中存活，而荚膜转换突变株的效果更为明显。野生型和突变株在马血或菌血症的小鼠模型中，口腔链球菌的存活率没有明显差异。在所有模型中，除了在肺部模型中，肺炎链球菌 TIGR4 的存活率均高于口腔链球菌标准株或荚膜转换突变株，除了在肺部模型中，肺炎链球菌 TIGR4 和荚膜转换突变株之间没有观察到显著差异。因此，我们确定了荚膜在口腔链球菌中具有保护功能的条件。在这些条件下，通过荚膜转换为 4 型可以增强口腔链球菌对清除的抗性，但增强程度低于毒力更强的肺炎链球菌 TIGR4 菌株。
