Sword and shield:: Linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense
Sword and shield:: Linked group B streptococcal β-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense
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DOI：
10.1073/pnas.0406143101
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发表时间：
2004-10-05
影响因子：
11.1
通讯作者：
Nizet, V
中科院分区：
文献类型：
--
作者：
Liu, GY;Doran, KS;Nizet, V
B 族链球菌 (GBS) 是新生儿肺炎、菌血症和脑膜炎的主要原因，并被发现持续存在于宿主吞噬细胞内。由 cylE 编码的成孔 GBS β-溶血素/溶细胞素 (betaH/C) 是一种重要的毒力因子，如多种体内模型所示。有趣的是，cylE 缺失不仅导致 betaH/C 活性丧失，而且还导致功能未知的类胡萝卜素色素丧失。在这项研究中，我们试图确定 cylE 可能有助于 GBS 吞噬细胞抵抗和增加毒力潜力的机制。我们发现，cylE 缺陷的 GBS 更容易从小鼠血流、人全血以及分离的巨噬细胞和中性粒细胞培养物中清除。存活与 betaH/C 诱导吞噬细胞溶解和凋亡的能力有关。在较低的细菌接种量下，cylE 还有助于增强吞噬细胞内的存活率，这归因于类胡萝卜素能够保护 GBS 免受氧化损伤。在氧化剂杀灭试验中，cylE 突变体被证明对过氧化氢、次氯酸盐、超氧化物和单线态氧更敏感。总之，这些数据表明了一种机制，通过该机制，相关的 cylE 编码表型、βH/C（剑）和类胡萝卜素（盾）共同作用，挫败免疫吞噬防御。
Group B Streptococcus (GBS) is a major cause of pneumonia, bacteremia, and meningitis in neonates and has been found to persist inside host phagocytic cells. The pore-forming GBS beta-hemolysin/ cytolysin (betaH/C) encoded by cylE is an important virulence factor as demonstrated in several in vivo models. Interestingly, cylE deletion results not only in the loss of betaH/C activity, but also in the loss of a carotenoid pigment of unknown function. in this study, we sought to define the mechanism(s) by which cylE may contribute to GBS phagocyte resistance and increased virulence potential. We found that cylE-deficient GBS was more readily cleared from a mouse's bloodstream, human whole blood, and isolated macrophage and neutrophil cultures. Survival was linked to the ability of betaH/C to induce cytolysis and apoptosis of the phagocytes. At a lower bacterial inoculum, cylE also contributed to enhanced survival within phagocytes that was attributed to the ability of carotenoid to shield GBS from oxidative damage. In oxidant killing assays, cylE mutants were shown to be more susceptible to hydrogen peroxide, hypochlorite, superoxide, and singlet oxygen. Together, these data suggest a mechanism by which the linked cylE-encoded phenotypes, betaH/C (sword) and carotenoid (shield), act in partnership to thwart the immune phagocytic defenses.