An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds
An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds
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DOI：
10.1371/journal.ppat.1000009
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发表时间：
2008-02-01
期刊：
影响因子：
6.7
通讯作者：
Bergstrom, Sven
中科院分区：
文献类型：
--
作者：
Bunikis, Ignas;Denker, Katrin;Bergstrom, Sven
伯氏疏螺旋体由于其感染各种生物体的能力而在广泛不同的环境中茁壮成长的能力是显著的。与肠道革兰氏阴性菌相比，这些螺旋体只有少数跨膜蛋白，其中一些被认为在溶质和营养物的摄取以及有毒物质的排泄中起作用。在这里，我们已经确定了外膜蛋白，BesC，这是一个假定的出口系统，包括组件BesA，BesB和BesC的一部分。我们发现，BesC，TolC同源物，形成通道的平面脂质双层，并参与抗生素耐药性。besC基因敲除不能在小鼠中建立感染，这表明了这种外膜通道在哺乳动物宿主中的重要性。BesC的生物物理特性可以用基于通道-隧道结构的模型来解释。我们还产生了一个结构模型的外排装置显示推定的空间方向BesC相对于AcrAB同系物BesAB。我们相信，我们的研究结果将有助于解开疏螺旋体的致病机制，以及在开发新的治疗药物，旨在阻止这种分泌装置的功能。
Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel-tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus.