PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin
PspA protects Streptococcus pneumoniae from killing by apolactoferrin, and antibody to PspA enhances killing of pneumococci by apolactoferrin
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DOI：
10.1128/iai.72.9.5031-5040.2004
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发表时间：
2004-09-01
影响因子：
3.1
通讯作者：
Briles, DE
中科院分区：
文献类型：
--
作者：
Shaper, M;Hollingshead, SK;Briles, DE
乳铁蛋白通过其铁螯合、杀菌活性和免疫调节活性而成为先天免疫的重要组成部分。脱铁乳铁蛋白 (ALF) 是乳铁蛋白的贫铁形式，对肺炎球菌和其他几种细菌具有杀菌作用。我们观察到乳铁蛋白 (LFN) 是一种来自乳铁蛋白 N 末端的 11 个氨基酸肽，对肺炎链球菌具有杀菌作用。肺炎链球菌菌株对 ALF 的敏感性各不相同。乳铁蛋白通过肺炎球菌表面蛋白 A (PspA) 与肺炎球菌表面结合。使用四种不同菌株的突变型 PspA(-) 肺炎球菌，我们观察到 PspA 对 ALF 的杀伤作用具有显着的保护作用。其他两种胆碱结合蛋白（PspC 和 PcpA）的基因敲除突变并不影响 ALF 的杀伤作用。 PspA 不必附着在细菌表面来抑制杀伤，因为 PspA 的可溶性重组 N 端一半可以防止 ALF 和 LFN 的杀伤。 PspA 的 11 个氨基酸片段也能够减少 LFN 的杀伤作用。 PspA 抗体可增强乳铁蛋白的杀伤作用。这些发现表明 ALF 与 PspA 的结合可能会阻断 ALF 负责杀伤的活性位点。
Lactoferrin is an important component of innate immunity through its sequestration of iron, bactericidal activity, and immune modulatory activity. Apollactoferrin (ALF) is the iron-depleted form of lactoferrin and is bactericidal against pneumococci and several other species of bacteria. We observed that lactoferricin (LFN), an 11-amino-acid peptide from the N terminus of lactoferrin, is bactericidal for Streptococcus pneumoniae. Strains of S. pneumoniae varied in their susceptibility to ALF. Lactoferrin is bound to the pneumococcal surface by pneumococcal surface protein A (PspA). Using mutant PspA(-) pneumococci of four different strains, we observed that PspA offers significant protection against killing by ALF. Knockout mutations in genes for two other choline-binding proteins (PspC and PcpA) did not affect killing by ALF. PspA did not have to be attached to the bacterial surface to inhibit killing, because the soluble recombinant N-terminal half of PspA could prevent killing by both ALF and LFN. An 11-amino-acid fragment of PspA was also able to reduce the killing by LFN. Antibody to PspA enhanced killing by lactoferrin. These findings suggested that the binding of ALF to PspA probably blocks the active site(s) of ALF that is responsible for killing.