Streptococcus pneumoniae clonal complex 199: genetic diversity and tissue-specific virulence.
Streptococcus pneumoniae clonal complex 199: genetic diversity and tissue-specific virulence.
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DOI：
10.1371/journal.pone.0018649
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发表时间：
2011-04-14
期刊：
影响因子：
3.7
通讯作者：
Pettigrew MM
中科院分区：
文献类型：
--
作者：
Thomas JC;Figueira M;Fennie KP;Laufer AS;Kong Y;Pichichero ME;Pelton SI;Pettigrew MM
肺炎链球菌是中耳炎的重要致病菌和侵袭性疾病。自从引入七价肺炎球菌结合疫苗以来，由于血清型19 A克隆复合物（CC）199分离株引起的替代疾病有所增加。本研究的目的是：1）描述19个CC 199分离株的遗传多样性，2）比较CC 199 19 A（n = 3）和15 B/C（n = 2）分离株在栗鼠模型中的肺炎球菌疾病，3）确定辅助基因与组织特异性疾病中的一个更大的收集S。 肺炎分离株。CC 199菌株进行比较基因组杂交分析。其中127个基因是完全存在的。CC 199菌株群分为两个主要分支，一个主要由携带分离株组成，另一个主要由疾病分离株组成。在灰鼠模型中，不同血清型的动物定植和致病的能力没有差异。然而，与携带分支分离株相比，来自疾病分支的分离株与更快的菌血症时间相关。一个19 A分离株表现出超强毒力。通过对应分析确定了12个组织特异性基因/区域。在筛选了326个分离株的不同集合后，spr 0282与携带相关。其中SP 0163、SP 0463、SPN 05002和RD 8a四个基因/区域与中耳分离株相关。SPN 05002也与血液和CSF相关，而RD 8a与血液分离株相关。使用Solexa配对末端测序平台对高毒力分离株的基因组进行测序，并与参考血清型19 A分离株的基因组进行比较，揭示存在与噬菌体基因具有序列相似性的新的20 kb区域。血清型以外的遗传因素可能调节CC 199的毒力潜力。这些研究对结合疫苗的长期有效性有影响。理想情况下，未来的疫苗将针对常见蛋白质，以有效减少接种疫苗人群的携带和疾病。
Streptococcus pneumoniae is an important cause of otitis media and invasive disease. Since introduction of the heptavalent pneumococcal conjugate vaccine, there has been an increase in replacement disease due to serotype 19A clonal complex (CC)199 isolates. The goals of this study were to 1) describe genetic diversity among nineteen CC199 isolates from carriage, middle ear, blood, and cerebrospinal fluid, 2) compare CC199 19A (n = 3) and 15B/C (n = 2) isolates in the chinchilla model for pneumococcal disease, and 3) identify accessory genes associated with tissue-specific disease among a larger collection of S. pneumoniae isolates. CC199 isolates were analyzed by comparative genome hybridization. One hundred and twenty-seven genes were variably present. The CC199 phylogeny split into two main clades, one comprised predominantly of carriage isolates and another of disease isolates. Ability to colonize and cause disease did not differ by serotype in the chinchilla model. However, isolates from the disease clade were associated with faster time to bacteremia compared to carriage clade isolates. One 19A isolate exhibited hypervirulence. Twelve tissue-specific genes/regions were identified by correspondence analysis. After screening a diverse collection of 326 isolates, spr0282 was associated with carriage. Four genes/regions, SP0163, SP0463, SPN05002 and RD8a were associated with middle ear isolates. SPN05002 also associated with blood and CSF, while RD8a associated with blood isolates. The hypervirulent isolate's genome was sequenced using the Solexa paired-end sequencing platform and compared to that of a reference serotype 19A isolate, revealing the presence of a novel 20 kb region with sequence similarity to bacteriophage genes. Genetic factors other than serotype may modulate virulence potential in CC199. These studies have implications for the long-term effectiveness of conjugate vaccines. Ideally, future vaccines would target common proteins to effectively reduce carriage and disease in the vaccinated population.
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