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甘露吡喃糖苷糖脂抑制分枝杆菌和生物膜生长,并增强分枝杆菌中的异烟肼抑制活性。

Mannopyranoside Glycolipids Inhibit Mycobacterial and Biofilm Growth and Potentiate Isoniazid Inhibition Activities in M. smegmatis.

机构信息

Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560 012, India.

Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India.

出版信息

Chembiochem. 2019 Aug 1;20(15):1966-1976. doi: 10.1002/cbic.201900040. Epub 2019 Jun 26.

Abstract

Lipomannan and lipoarabinomannan are integral components of the mycobacterial cell wall. Earlier studies demonstrated that synthetic arabinan and arabinomannan glycolipids acted as inhibitors of mycobacterial growth, in addition to exhibiting inhibitory activities of mycobacterial biofilm. Herein, it is demonstrated that synthetic mannan glycolipids are better inhibitors of mycobacterial growth, whereas lipoarabinomannan has a higher inhibition efficiency to biofilm. Syntheses of mannan glycolipids with a graded number of mannan moieties and an arabinomannan glycolipid are conducted by chemical methods and subsequent mycobacterial growth and biofilm inhibition studies are conducted on Mycobacterium smegmatis. Growth inhibition of (73±3) % is observed with a mannose trisaccharide containing a glycolipid, whereas this glycolipid did not promote biofilm inhibition activity better than that of arabinomannan glycolipid. The antibiotic supplementation activities of glycolipids on growth and biofilm inhibitions are evaluated. Increases in growth and biofilm inhibitions are observed if the antibiotic is supplemented with glycolipids, which leads to a significant reduction of inhibition concentrations of the antibiotic.

摘要

脂阿拉伯甘露聚糖和脂阿拉伯甘露聚糖是分枝杆菌细胞壁的组成部分。早期研究表明,合成阿拉伯聚糖和阿拉伯甘露聚糖糖脂除了具有抑制分枝杆菌生物膜的活性外,还能抑制分枝杆菌的生长。本文证明了合成甘露聚糖糖脂是更好的分枝杆菌生长抑制剂,而脂阿拉伯甘露聚糖对生物膜具有更高的抑制效率。通过化学方法合成具有不同甘露糖单元数量的甘露聚糖糖脂和阿拉伯甘露聚糖糖脂,并在耻垢分枝杆菌上进行分枝杆菌生长和生物膜抑制研究。含甘露糖三糖的糖脂的生长抑制率为(73±3)%,而该糖脂的生物膜抑制活性并不优于阿拉伯甘露聚糖糖脂。还评估了糖脂对生长和生物膜抑制的抗生素补充活性。如果将抗生素与糖脂一起补充,则会观察到生长和生物膜抑制的增加,这导致抗生素的抑制浓度显著降低。

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