Identification of invasive serotype 1 pneumococcal isolates that express nonhemolytic pneumolysin
Identification of invasive serotype 1 pneumococcal isolates that express nonhemolytic pneumolysin
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DOI：
10.1128/jcm.44.1.151-159.2006
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发表时间：
2006-01-01
影响因子：
9.4
通讯作者：
Mitchell, TJ
中科院分区：
文献类型：
--
作者：
Kirkham, LAS;Jefferies, JMC;Mitchell, TJ
最近，在整个欧洲，由血清型I肺炎链球菌引起的侵袭性肺炎球菌病（IPD）有所增加。血清型I IPD与欧洲和北美的菌血症和肺炎相关，尤其是在新生儿中，并且在至少10个国家中被列为前五个最流行的肺炎球菌血清型。目前批准的小儿肺炎球菌疫苗对这种血清型没有保护作用。对252株临床分离的沙门氏菌进行了筛选。在研究组中，我们发现了存在于研究组中的四种血清型I菌株中的两种的肺炎球菌溶血素基因突变。对来自不同苏格兰卫生委员会的IPD患者的另外28个血清型I分离株的分析显示，> 50%在其肺炎球菌溶血素基因中具有突变。这导致肺炎球菌溶血素的非溶血形式的表达。所有产生非溶血性肺炎球菌溶血素的菌株均为序列型306（ST 306），而产生“野生型”肺炎球菌溶血素的菌株为ST 227。这些突变位于参与孔形成的肺炎球菌溶血素区域。这些突变可以在体外进行，以产生非溶血性表型。链球菌溶血素在所有血清型的链球菌中通常是保守的。血清型ST 306是肺炎链球菌溶血素，并且对于完全侵袭性疾病是必需的;然而，似乎血清型I ST 306不需要溶血活性肺炎链球菌溶血素来引起1 PD。
Recently, there has been an increase in invasive pneumococcal disease (IPD) caused by serotype I Streptococcus pneumoniae throughout Europe. Serotype I IPD is associated with bacteremia and pneumonia in Europe and North America, especially in neonates, and is ranked among the top five most prevalent pneumococcal serotypes in at least 10 countries. The currently licensed pediatric pneumococcal vaccine does not afford protection to this serotype. Upon screening of 252 clinical isolates of S. pneumoniae, we discovered mutations in the pneumolysin gene of two out of the four serotype I strains present in the study group. Analysis of an additional 28 serotype I isolates from patients with IPD front various Scottish Health Boards, revealed that > 50% had mutations in their pneumolysin genes. This resulted in the expression of nonhemolytic forms of pneumolysin. All of the strains producing nonhemolytic pneumolysin were sequence type 306 (ST306), whereas those producing "wild-type" pneumolysin were ST227. The mutations were in a region of pneumolysin involved in pore formation. These mutations can be made in vitro to give the nonhemolytic phenotype. Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype I ST306 does not require hemolytically active pneumolysin to cause 1PD.