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葡萄糖类似物甲基葡萄糖对表皮葡萄球菌生物被膜形成的影响及调节机制的研究

Effect of glucose analogs on bofilm and expressions of related genes in Staphylococcus epidermidis

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【作者】 靳嘉巍; 查锡良; 李华林; 瞿涤;

【Author】 JIN Jia-wei1 ZHA Xi-liang 1* LI Hua-lin2 QU Di2( 1Key Laboratory of Glycoconjugate Research, Ministry of Public Health, Department of Biochemistry and Molecular Biology, 2Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China)

【机构】 复旦大学上海医学院生物化学与分子生物学系卫生部糖复合物重点实验室; 复旦大学上海医学院教育部医学分子病毒学重点实验室; 复旦大学上海医学院教育部医学分子病毒学重点实验室 上海200032; 上海200032; 上海200032;

【摘要】 生物被膜(Biofilm)是条件致病菌表皮葡萄球菌(Staphylococcusepidermidis)的主要致病因素,生物被膜的形成依赖多糖PIA的合成,PIA合成与细菌糖代谢相关。通过研究葡萄糖类似物甲基葡萄糖(MethylDglucoside,MG)对生物被膜的形成及相关基因表达的影响,考察生物被膜形成的调控机制并寻找抑制生物被膜形成的方法。甲基葡萄糖能抑制97337株生物被膜的形成,而且不同浓度的甲基葡萄糖对生物膜作用不同。甲基葡萄糖对97337株生物被膜形成的早期的粘附有较强的抑制作用;不同浓度的甲基葡萄糖处理后对ica和AtlE基因的mRNA表达水平影响不大,但能诱导agr基因的表达,这与甲基葡萄糖处理不同时间后的结果一致;而且甲基葡萄糖处理后97337的表面相关蛋白的组成明显改变。甲基葡萄糖对生物膜的抑制并不直接由于它对生长的抑制,它对细菌生长和生物被膜形成的抑制与其在细菌糖代谢中的竞争性相关;甲基葡萄糖能通过调控agr基因的表达改变细菌表面从而抑制97337的早期粘附和生物被膜的形成,但没有通过调控icaADBC、icaR的表达抑制生物膜的形成,可能与其对合成PIA相关糖基转移酶的竞争性抑制相关。

【Abstract】 Staphylococcus epidermidis, an opportunistic human pathogen, has become the most important cause of nosocomial infections in recent years. Its infection is mainly due to the ability to form biofilm on indwelling medical devices. To investigate the response mechanism of S. epidermidis to environment in biofilm formation and find efficient anti-biofilm methods, we investigated effects of two glucose analogs, 2-Deoxy-D-glucose (2DG) and Methyl-D-glucoside (MG), on biofilm formation, expression of related gene and changes of surface protein in S. epidermidis 97-337 with high biofilm formation capability and pathogenicity. The effect of MG on biofilm formation was more complex than that of 2-DG which is a strong inhibitor in S. epidermidis 97-337 growth. MG can induce biofilm formation of S. epidermidi 97-337 in low concentration and exhibited strong inhibition only in high concentration, and distinctly inhibited the primary attachment to poly-material. In S. epidermidi 97-337 cultured in media with MG, expressions of ica and AtlE were not be changed obviously in mRNA level, but mRNA expression of agr gene increased distinctly, and MG disturbed component of surface proteins of S. epidermidi 97-337. Glucose analogies MG can inhibit S. epidermidi 97-337 biofilm formation, and MG inhibition in initiating attachment dramatically contributes to it. MG inhibition effects result not from regulating the expression of ica and AtlE genes but from changing the protein components on surface by regulating agr gene expression, and it can be presumed that MG’s competitive character in bacteria glycose metabolism is crucial factor for these effects.

【基金】 国家“863计划”(2001AA223011)~~
  • 【文献出处】 微生物学报 ,Acta Microbiologica Sinica , 编辑部邮箱 ,2005年06期
  • 【分类号】Q935
  • 【被引频次】6
  • 【下载频次】253
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