Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis
Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis
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DOI：
10.1128/iai.69.2.949-958.2001
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发表时间：
2001-02-01
影响因子：
3.1
通讯作者：
Johnson, S
中科院分区：
文献类型：
--
作者：
Adamou, JE;Heinrichs, JH;Johnson, S
从肺炎链球菌基因组序列中鉴定出4个肺炎球菌基因（phtA、phtB、phtD和phtE），它们编码一个新的同源蛋白家族（32%至87%的同一性）。这些开放阅读框被选择为潜在的疫苗候选物，基于它们拥有的疏水前导序列，推测这些蛋白质靶向细菌细胞表面。这些基因产物的推导的氨基酸序列的分析揭示了组氨酸三联体基序（HxxHxH）的存在，称为Pht（肺炎球菌组氨酸三联体），其在四种蛋白质中的每一种中保守并重复数次。四个pht基因（phtA，phtB，phtD和phtE的截短版本）在大肠杆菌中表达。基于流式细胞术的测定证实，PhtA，PhtB，PhtD和在较小程度上，PhtE在完整细菌的表面上是可检测的。重组PhtA、PhtB和PhtD在全身性疾病的小鼠模型中引起针对某些肺炎球菌荚膜类型的保护。这些新的肺炎球菌抗原可作为有效的疫苗。最流行的肺炎球菌血清型。
Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified front the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface, Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against. the most prevalent pneumococcal serotypes.