Department of Microbiology, Tumor, and Cell Biology.
J Infect Dis. 2014 Feb 1;209(3):377-88. doi: 10.1093/infdis/jit481. Epub 2013 Sep 5.
Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated.
A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed.
Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness.
Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children.
肺炎球菌血清型由具有不同遗传成分的数量不等的克隆谱系代表，这可能会影响侵袭性。然而，同一遗传谱系内的遗传变异可能比预期的要大。
使用脉冲场凝胶电泳（PFGE）和多位点序列分型对同一地区同一时期的 715 例侵袭性和携带性分离株进行了比较。对细菌基因组测序、功能检测和体内毒力小鼠研究进行了比较。
同一血清型的克隆类型，但同一克隆复合体（CC）内的克隆内变体在侵袭性疾病的潜力上存在差异。常见的 CC138 分为几种 PFGE 模式，部分原因是温和噬菌体的数量、位置和类型。对 4 株具有不同侵袭性疾病潜力的 CC138 分离株进行全基因组测序，揭示了与毒力相关的蛋白肺炎球菌表面蛋白 A（PspA）和肺炎球菌胆碱结合蛋白 C（PspC）的克隆内序列变异。缺乏 PcpA 的携带株在小鼠中表现出较低的毒力，并且根据侵袭性，人因子 H 的结合存在差异。
肺炎球菌的克隆类型，甚至是克隆内变体，在儿童中表现出不同的侵袭性疾病潜力。反映不同前噬菌体含量的克隆内变体在主要表面抗原上存在差异。这表明持续的免疫选择，例如由于 PspC 介导的补体抵抗通过不同的人因子 H 结合，可能会影响儿童的侵袭性。
