Regions of diversity 8, 9 and 13 contribute to Streptococcus pneumoniae virulence
Regions of diversity 8, 9 and 13 contribute to Streptococcus pneumoniae virulence
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DOI：
10.1186/1471-2180-7-80
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发表时间：
2007-08-27
期刊：
影响因子：
4.2
通讯作者：
Orihuela, Carlos J.
中科院分区：
文献类型：
--
作者：
Embry, Addie;Hinojosa, Ernesto;Orihuela, Carlos J.
背景：肺炎链球菌是社区获得性肺炎的主要病因。以前，使用比较基因组分析，13个区域的基因组可塑性已确定在S。pneumoniae基因组。这些“多样性区域”（RD）占所有测试的肺炎球菌中观察到的基因组变异的一半，此外，被确定为编码各种推定的毒力因子。迄今为止，已明确证明5个RD内的基因有助于S。肺炎毒力目前尚不清楚是否剩余的RD也有助于毒力。pneumoniae突变体的RD 2、5、7、8、9、12和13缺陷。RD 8、9和13缺陷的突变体在疾病的小鼠模型中减毒。RD 8全长40,358个核苷酸，编码37个基因。使用一组同基因突变体，我们确定RD 8b 3是RD 8内负责毒力的操纵子。与感染野生型的小鼠相比，感染RD 8、RD 8b 3、RD 9和RD 13缺陷突变体的小鼠在鼻内攻击后两天血液中的细菌显著减少，并且随着时间的推移存活率提高。在所有的情况下，突变体定殖鼻咽相当于野生型。结论：RD 1，3，4，6和10内的基因已被证明有助于毒力。这项研究表明，RD 8，9和13内的基因也有助于毒力。RD 2、5、7、8、9、12和13缺陷突变体定殖鼻咽的能力表明，这些RD内的基因对于无症状携带是不需要的。尽管如此，RD 8b 3、9和13缺陷突变体被减毒的观察结果表明，这些基因座内的基因对于细菌越过鼻咽传播到正常无菌部位是必需的。
Background: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. Previously, using comparative genomic analyses, 13 regions of genomic plasticity have been identified in the S. pneumoniae genome. These "Regions of Diversity" (RDs) accounted for half the genomic variation observed amongst all pneumococci tested, moreover, were determined to encode a variety of putative virulence factors. To date, genes within 5 RDs have been unequivocally demonstrated to contribute to S. pneumoniae virulence. It is unknown if the remaining RDs also contribute to virulence.Results: Using allelic exchange, we created S. pneumoniae mutants that were deficient in RD2, 5, 7, 8, 9, 12 and 13. Mutants deficient in RD8, 9 and 13 were attenuated in a mouse model of disease. RD8 is 40,358 nucleotides in length and encodes 37 genes. Using a panel of isogenic mutants, we determined that RD8b3 is the operon within RD8 that is responsible for virulence. Mice infected with mutants deficient in RD8, RD8b3, RD9 and RD13 had significantly less bacteria in the blood two days after intranasal challenge and improved survival over time versus mice infected with wild type. In all instances mutants colonized the nasopharynx at levels equivalent to wild type.Conclusion: Genes within RD1, 3, 4, 6, and 10 have previously been shown to contribute to virulence. This study demonstrates that genes within RD8, 9 and 13 also contribute to virulence. The ability of mutants deficient in RD2, 5, 7, 8, 9, 12, and 13 to colonize the nasopharynx indicates that genes within these RDs are not required for asymptomatic carriage. Nonetheless, the observation that mutants deficient in RD8b3, 9 and 13 are attenuated indicates that genes within these loci are necessary for spread of the bacteria beyond the nasopharynx to normally sterile sites.