Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis
Streptococcus pneumoniae surface protein PcpA elicits protection against lung infection and fatal sepsis
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DOI：
10.1128/iai.01126-07
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发表时间：
2008-06-01
影响因子：
3.1
通讯作者：
Briles, David E.
中科院分区：
文献类型：
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作者：
Glover, David T.;Hollingshead, Susan K.;Briles, David E.
先前的研究表明，肺炎球菌胆碱结合蛋白A （PcpA）对肺炎链球菌的全毒力很重要，其氨基酸序列表明它可能在细胞粘附中发挥作用。PcpA受锰依赖调节剂的控制，仅在低锰浓度下表达，类似于血液和肺部的锰浓度。PcpA的表达在高锰浓度下被抑制，类似于在分泌物中发现的。在这项研究中，我们已经证明PcpA在肺炎和脓毒症小鼠模型中具有统计学意义的保护作用。在四种攻毒菌株的肺炎模型中，与仅接种明矾的小鼠相比，接种PcpA和明矾的小鼠肺部回收的肺炎链球菌细胞在统计学上较少。免疫使CFU中位数降低了4- 400倍（平均为28倍）。在TIGR4菌株的脓毒症模型中，PcpA表达导致死亡时间缩短，PcpA皮下免疫可提高表达PcpA的野生型肺炎球菌感染小鼠的存活时间。
Previous studies have suggested that pneumococcal choline binding protein A (PcpA) is important for the full virulence of Streptococcus pneumoniae, and its amino acid sequence suggests that it may play a role in cellular adherence. PcpA is under the control of a manganese-dependent regulator and is only expressed at low manganese concentrations, similar to those found in the blood and lungs. PcpA expression is repressed under high manganese concentrations, similar to those found in secretions. In this study, we have demonstrated that PcpA elicits statistically significant protection in murine models of pneumonia and sepsis. In the model of pneumonia with each of four challenge strains, statistically fewer S. pneumoniae cells were recovered from the lungs of mice immunized with PcpA and alum versus mice immunized with alum only. The immunizations reduced the median CFU by 4- to 400-fold (average of 28-fold). In the model of sepsis using strain TIGR4, PcpA expression resulted in shorter times to become moribund and subcutaneous immunization with PcpA increased survival times of mice infected with wild-type PcpA-expressing pneumococci.