Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.
Biol Pharm Bull. 2011;34(6):917-20. doi: 10.1248/bpb.34.917.
Formation of biofilm in pathogenic bacteria defends them from antibiotics and the immune system of a host's life. Hence, investigation of the molecular mechanisms of biofilm formation and search for new substances counteracting this formation are becoming an attractive research area. In the course of our search for new inhibitors of biofilm formation in Mycobacterium species, we rediscovered a cyclic trihydroxamate siderophore, desferrioxamine E, from the culture of the marine-derived Actinomycete MS67. Desferrioxamine E inhibited biofilm formation of Mycobacterium smegmatis and M. bovis BACILLE de CALMETTE et GUÉRIN (BCG) with minimum inhibitory concentration (MIC) value of 10 µM, while no anti-microbial activity was observed up to 160 µM. Desferrioxamine E was also able to restore the anti-microbial activity of isoniazid against M. smegmatis by inhibiting biofilm formation. Mechanistic analysis of desferrioxamine E suggested that such inhibition might come from the depletion of iron in the medium, which is essential for biofilm formation in Mycobacterium species.
生物膜的形成使病原菌能够抵御抗生素和宿主免疫系统的攻击。因此,研究生物膜形成的分子机制以及寻找新的物质来对抗这种形成,正成为一个极具吸引力的研究领域。在我们寻找分枝杆菌属中新的生物膜形成抑制剂的过程中,我们从海洋来源的放线菌 MS67 的培养物中重新发现了一种环状三羟肟酸铁载体,去铁胺 E。去铁胺 E 以 10µM 的最小抑菌浓度(MIC)值抑制了耻垢分枝杆菌和牛分枝杆菌卡介苗(BCG)的生物膜形成,而在高达 160µM 时没有观察到抗微生物活性。去铁胺 E 还能够通过抑制生物膜形成来恢复异烟肼对耻垢分枝杆菌的抗菌活性。去铁胺 E 的机制分析表明,这种抑制可能来自于培养基中铁的耗尽,这对于分枝杆菌属的生物膜形成是必不可少的。