Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells.
Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to endothelial and epithelial cells.
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DOI：
10.1038/srep37758
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发表时间：
2016-11-28
影响因子：
4.6
通讯作者：
Wygrecka M
中科院分区：
文献类型：
--
作者：
Zakrzewicz D;Bergmann S;Didiasova M;Giaimo BD;Borggrefe T;Mieth M;Hocke AC;Lochnit G;Schaefer L;Hammerschmidt S;Preissner KT;Wygrecka M
肺炎链球菌是社区获得性肺炎最常见的原因。感染过程涉及细菌细胞表面受体，其与宿主细胞外基质组分相互作用以促进细菌的定殖和传播。在这里，我们研究了宿主来源的胞外RNA（eRNA）在肺炎球菌肺泡上皮细胞感染过程中的作用。我们的研究表明，eRNA剂量依赖性地增加S。肺炎侵入肺泡上皮细胞。胞外烯醇化酶（Eno）是一种纤溶酶原（Plg）受体，是S. pneumoniae表面，和6个Eno eRNA结合位点，包括C-末端15个氨基酸基序，含有赖氨酸残基434。虽然赖氨酸434取代甘氨酸（K434 G）显著降低了eRNA与Eno的结合，但S.携带C-末端赖氨酸缺失和内部Plg结合基序突变的肺炎菌株仅轻微受损。因此，使用质谱方法，我们确定了7个新的eRNA结合蛋白在肺炎球菌细胞壁。鉴于肺炎球菌上存在大量的eRNA相互作用蛋白，RNase 1治疗完全抑制了eRNA介导的肺炎球菌肺泡上皮细胞感染。我们的数据支持进一步努力使用RNAse 1作为抗微生物剂来对抗肺炎球菌感染性疾病。
Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. The infection process involves bacterial cell surface receptors, which interact with host extracellular matrix components to facilitate colonization and dissemination of bacteria. Here, we investigated the role of host-derived extracellular RNA (eRNA) in the process of pneumococcal alveolar epithelial cell infection. Our study demonstrates that eRNA dose-dependently increased S. pneumoniae invasion of alveolar epithelial cells. Extracellular enolase (Eno), a plasminogen (Plg) receptor, was identified as a novel eRNA-binding protein on S. pneumoniae surface, and six Eno eRNA-binding sites including a C-terminal 15 amino acid motif containing lysine residue 434 were characterized. Although the substitution of lysine 434 for glycine (K434G) markedly diminished the binding of eRNA to Eno, the adherence to and internalization into alveolar epithelial cells of S. pneumoniae strain carrying the C-terminal lysine deletion and the mutation of internal Plg-binding motif were only marginally impaired. Accordingly, using a mass spectrometric approach, we identified seven novel eRNA-binding proteins in pneumococcal cell wall. Given the high number of eRNA-interacting proteins on pneumococci, treatment with RNase1 completely inhibited eRNA-mediated pneumococcal alveolar epithelial cell infection. Our data support further efforts to employ RNAse1 as an antimicrobial agent to combat pneumococcal infectious diseases.
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影响因子：
3.6
作者：
Bergmann, S;Wild, D;Hammerschmidt, S
通讯作者：
Hammerschmidt, S
影响因子：
3.8
作者：
Anderton, Julie M.;Rajam, Gowrisankar;Ades, Edwin W.
通讯作者：
Ades, Edwin W.
影响因子：
20.3
作者：
Fischer, Silvia;Gerriets, Tibo;Preissner, Klaus T.
通讯作者：
Preissner, Klaus T.
影响因子：
6.7
作者：
Fischer, Silvia;Grantzow, Tobias;Deindl, Elisabeth
通讯作者：
Deindl, Elisabeth
影响因子：
3.6
作者：
Holmes, AR;McNab, R;Jenkinson, HF
通讯作者：
Jenkinson, HF