Identification of a candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease
Identification of a candidate Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease
复制标题
DOI：
10.1128/iai.00316-06
复制
发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Orihuela, Carlos J.
中科院分区：
文献类型：
--
作者：
Obert, Caroline;Sublett, Jack;Orihuela, Carlos J.
肺炎链球菌是社区获得性肺炎和革兰氏阳性败血症的主要原因。虽然已经确定了多个毒力决定因素，但决定分离物引起侵袭性肺炎球菌病（IPD）倾向的特征组合仍然未知。在这项研究中，我们通过比较基因组杂交确定了42例侵袭性和30例非侵袭性临床分离株血清型6A、6B和14的遗传组成。存在/缺失基因矩阵的比较（即比较基因组分析[CGA]）确定了一个候选核心基因组，包括1553个基因（占TIGR4基因组的73%），154个基因的存在与导致IPD的能力相关，176个基因的存在与非侵入性表型相关。通过CGA鉴定的基因与已发表的签名标记诱变研究交叉引用，用于鉴定体内传代所需的核心基因和ipd相关基因。其中鉴定出两个致病性岛，分别是编码神经氨酸酶和v型钠合酶的多样性区8a （RD8a）和编码戈氏链球菌血小板粘附素GspB同源蛋白PsrP的RD10。感染PsrP突变体的小鼠发生菌血症的时间延迟，与野生型感染对照相比，死亡率降低。最后，确定了7种rd的存在与非侵入性表型相关，这一发现表明一些rd可能有助于无症状定植。综上所述，RDs在侵袭性和非侵袭性分离株之间分布不均，RD8a和RD10与分离株引起IPD的倾向相关，PsrP是小鼠完全毒力所必需的。
Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and gram-positive sepsis. While multiple virulence determinants have been identified, the combination of features that determines the propensity of an isolate to cause invasive pneumococcal disease (IPD) remains unknown. In this study, we determined the genetic composition of 42 invasive and 30 noninvasive clinical isolates of serotypes 6A, 6B, and 14 by comparative genomic hybridization. Comparison of the present/absent gene matrix (i.e., comparative genomic analysis [CGA]) identified a candidate core genome consisting of 1,553 genes (73% of the TIGR4 genome), 154 genes whose presence correlated with the ability to cause IPD, and 176 genes whose presence correlated with the noninvasive phenotype. Genes identified by CGA were cross-referenced with the published signature-tagged mutagenesis studies, which served to identify core and IPD-correlated genes required for in vivo passage. Among these, two pathogenicity islands, region of diversity 8a (RD8a), which encodes a neuraminidase and V-type sodium synthase, and RD10, which encodes PsrP, a protein homologous to the platelet adhesin GspB in Streptococcus gordonii, were identified. Mice infected with a PsrP mutant were delayed in the development of bacteremia and demonstrated reduced mortality versus wild-type-infected controls. Finally, the presence of seven RDs was determined to correlate with the noninvasive phenotype, a finding that suggests some RDs may contribute to asymptomatic colonization. In conclusion, RDs are unequally distributed between invasive and noninvasive isolates, RD8a and RD10 are correlated with the propensity of an isolate to cause IPD, and PsrP is required for full virulence in mice.