Glycosaminoglycans are involved in bacterial adherence to lung cells.
Glycosaminoglycans are involved in bacterial adherence to lung cells.
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DOI：
10.1186/s12879-017-2418-5
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发表时间：
2017-05-02
影响因子：
3.7
通讯作者：
García B
中科院分区：
文献类型：
--
作者：
Rajas O;Quirós LM;Ortega M;Vazquez-Espinosa E;Merayo-Lloves J;Vazquez F;García B
下呼吸道感染是全球十大死亡原因之一。由于病原体与细胞的粘附是感染过程中的关键步骤，阻断真核受体和细菌配体之间的相互作用可能会使发病过程停止。众所周知，细胞表面糖胺聚糖（GAG）是多种细菌与不同细胞类型粘附的介质，因此研究它们在各种病原菌与肺细胞（包括上皮细胞和成纤维细胞）粘附中的作用非常有意义。通过抑制细胞表面 GAG 的生物合成和酶降解来降低其水平，以及与各种 GAG 的结合竞争实验，研究了细胞表面 GAG 在细菌粘附中的功能。通过与两种肽竞争来评估不同细菌粘附素参与附着的情况，这两种肽都含有共有的肝素结合序列。使用抗多糖蛋白聚糖和酶法去除磷脂酰肌醇蛋白聚糖进行阻断抑制测定，以测试它们对细菌粘附的参与。在与特异性脱硫肝素的竞争实验中研究了 GAG 精细结构在与病原体相互作用中的重要性。当两个肺细胞表面的 GAG 水平降低时，所有测试的细菌的结合都会减少。不同类型GAG的竞争实验表明，硫酸乙酰肝素链是主要参与的种类。细胞表面蛋白聚糖的阻断或去除证明多聚糖比磷脂酰肌醇发挥更重要的作用。该结合被包括肝素结合序列的肽部分抑制。脱硫肝素还可以不同程度地减少细菌粘附，具体取决于细菌和硫酸化残留物，特别是在成纤维细胞中。综上所述，这些数据表明细胞表面的 GAG 链参与细菌粘附素与肺细胞的粘附。硫酸乙酰肝素似乎是所涉及的主要种类，并且结合取决于分子的硫酸化模式。这些数据可以促进新的抗感染策略的开发，从而能够开发更有效地阻止病原体与肺细胞之间相互作用的新程序。
Lower respiratory infections are among the top ten causes of death worldwide. Since pathogen to cell adhesion is a crucial step in the infection progress, blocking the interaction between eukaryotic receptors and bacterial ligands may enable the pathogenesis process to be stopped. Cell surface glycosaminoglycans (GAGs) are known to be mediators in the adhesion of diverse bacteria to different cell types, making it of interest to examine their involvement in the attachment of various pathogenic bacteria to lung cells, including epithelial cells and fibroblasts. The function of cell surface GAGs in bacterial adhesion was studied by reducing their levels through inhibiting their biosynthesis and enzymatic degradation, as well as in binding competition experiments with various species of GAGs. The participation of the different bacterial adhesins in attachment was evaluated through competition with two peptides, both containing consensus heparin binding sequences. Blocking inhibition assays using anti-syndecans and the enzymatic removal of glypicans were conducted to test their involvement in bacterial adhesion. The importance of the fine structure of GAGs in the interaction with pathogens was investigated in competition experiments with specifically desulfated heparins. The binding of all bacteria tested decreased when GAG levels in cell surface of both lung cells were diminished. Competition experiments with different types of GAGs showed that heparan sulfate chains are the main species involved. Blocking or removal of cell surface proteoglycans evidenced that syndecans play a more important role than glypicans. The binding was partially inhibited by peptides including heparin binding sequences. Desulfated heparins also reduced bacterial adhesion to different extents depending on the bacterium and the sulfated residue, especially in fibroblast cells. Taken together, these data demonstrate that the GAG chains of the cell surface are involved in the adhesion of bacterial adhesins to lung cells. Heparan sulfate seems to be the main species implicated, and binding is dependent on the sulfation pattern of the molecule. These data could facilitate the development of new anti-infective strategies, enabling the development of new procedures for blocking the interaction between pathogens and lung cells more effectively.