Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity.
Streptococcus pneumoniae invades erythrocytes and utilizes them to evade human innate immunity.
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DOI：
10.1371/journal.pone.0077282
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kawabata S
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Terao Y;Mori-Yamaguchi Y;Domon H;Sakaue Y;Yagi T;Nishino K;Yamaguchi A;Nizet V;Kawabata S
肺炎链球菌是一种革兰氏阳性菌，是引起肺炎和败血症等侵袭性感染相关疾病的主要原因。在血液中，红细胞被认为是细菌生长的重要因素，因为它们含有丰富的营养物质。然而，S.肺炎和红细胞仍不清楚。我们分析了S.本发明的目的在于研究人红细胞中存在的铁离子对肺炎球菌和红细胞的影响，并且发现人红细胞中存在的铁离子支持金黄色葡萄球菌（另一种主要的革兰氏阳性脓毒症病原体）的生长，同时其通过产生自由基而部分抑制肺炎球菌的生长。S.对与人红细胞或血液一起孵育的肺炎杆菌细胞进行扫描电子和共聚焦荧光显微镜分析，其显示细菌细胞粘附并侵入人红细胞。此外，S.在来自侵袭性肺炎球菌感染患者的血液培养物中，发现肺炎球菌细胞与人红细胞相关。红细胞侵袭实验表明，含LPXTG基序的肺炎球菌蛋白、红细胞脂筏和红细胞肌动蛋白重塑都参与了侵袭机制。在中性粒细胞杀伤试验中，S.与红细胞共孵育的pneumoniae细胞比不与红细胞共孵育的pneumoniae细胞更高。H_2O_2对S.肺炎链球菌在红细胞存在下几乎完全无效。这些结果表明，即使当S.尽管铁离子诱导的自由基部分杀死了肺炎微生物，但它们仍然可以侵入红细胞。此外，在红细胞存在下，S.肺炎克雷伯氏菌可以更有效地逃避抗生素、嗜中性粒细胞吞噬作用和H2O2杀伤。
Streptococcus pneumoniae, a Gram-positive bacterium, is a major cause of invasive infection-related diseases such as pneumonia and sepsis. In blood, erythrocytes are considered to be an important factor for bacterial growth, as they contain abundant nutrients. However, the relationship between S. pneumoniae and erythrocytes remains unclear. We analyzed interactions between S. pneumoniae and erythrocytes, and found that iron ion present in human erythrocytes supported the growth of Staphylococcus aureus, another major Gram-positive sepsis pathogen, while it partially inhibited pneumococcal growth by generating free radicals. S. pneumoniae cells incubated with human erythrocytes or blood were subjected to scanning electron and confocal fluorescence microscopic analyses, which showed that the bacterial cells adhered to and invaded human erythrocytes. In addition, S. pneumoniae cells were found associated with human erythrocytes in cultures of blood from patients with an invasive pneumococcal infection. Erythrocyte invasion assays indicated that LPXTG motif-containing pneumococcal proteins, erythrocyte lipid rafts, and erythrocyte actin remodeling are all involved in the invasion mechanism. In a neutrophil killing assay, the viability of S. pneumoniae co-incubated with erythrocytes was higher than that without erythrocytes. Also, H2O2 killing of S. pneumoniae was nearly completely ineffective in the presence of erythrocytes. These results indicate that even when S. pneumoniae organisms are partially killed by iron ion-induced free radicals, they can still invade erythrocytes. Furthermore, in the presence of erythrocytes, S. pneumoniae can more effectively evade antibiotics, neutrophil phagocytosis, and H2O2 killing.
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影响因子：
3.6
作者：
Farrell, David J.;Klugman, Keith P.;Pichichero, Michael
通讯作者：
Pichichero, Michael
DOI：
10.1073/pnas.0608213104
发表时间：
2007-02-20
影响因子：
11.1
作者：
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通讯作者：
Wouters, Fred S.
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
4.2
作者：
Doherty, Conor P.
通讯作者：
Doherty, Conor P.
影响因子：
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作者：
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通讯作者：
Beall, Bernard W.