The Large Mechanosensitive Channel MscL Determines Bacterial Susceptibility to the Bacteriocin Sublancin 168
The Large Mechanosensitive Channel MscL Determines Bacterial Susceptibility to the Bacteriocin Sublancin 168
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DOI：
10.1128/aac.00439-09
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发表时间：
2009-11-01
影响因子：
4.9
通讯作者：
van Dijl, Jan Maarten
中科院分区：
文献类型：
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作者：
Kouwen, Thijs R. H. M.;Trip, Erik N.;van Dijl, Jan Maarten
枯草芽孢杆菌（Bacillus subtilis）菌株168产生极稳定的广谱抗生素subblancin 168。已知的亚蓝质168易感生物包括重要的病原体，如金黄色葡萄球菌。尽管如此，自发现以来，subblancin 168的作用方式仍然难以捉摸。因此，目前的研究旨在鉴定细菌对亚blancin 168敏感的细胞决定因素。平板培养和液体培养的生长抑制和竞争实验表明，亚blancin 168介导的枯草芽孢杆菌和金黄色葡萄球菌敏感细胞的生长抑制受生长培养基中NaCl浓度的影响。添加NaCl不影响subblancin 168的产生、活性和稳定性，但降低了敏感细胞对这种抗生素的敏感性。重要的是，枯草芽孢杆菌和金黄色葡萄球菌细胞对亚blancin 168的敏感性被证明取决于电导MscL的大机械敏感通道的存在。相比之下，MscL与细菌素nisin或Pep5的易感性无关。综上所述，我们前所未有的结果表明，MscL是细菌亚鞘蛋白168敏感性的关键和特异性决定因素，可能作为这种抗生素的直接靶点或进入细胞质的大门。
Bacillus subtilis strain 168 produces the extremely stable and broad-spectrum lantibiotic sublancin 168. Known sublancin 168-susceptible organisms include important pathogens, such as Staphylococcus aureus. Nevertheless, since its discovery, the mode of action of sublancin 168 has remained elusive. The present studies were, therefore, aimed at the identification of cellular determinants for bacterial susceptibility toward sublancin 168. Growth inhibition and competition assays on plates and in liquid cultures revealed that sublancin 168-mediated growth inhibition of susceptible B. subtilis and S. aureus cells is affected by the NaCl concentration in the growth medium. Added NaCl did not influence the production, activity, or stability of sublancin 168 but, instead, lowered the susceptibility of sensitive cells toward this lantibiotic. Importantly, the susceptibility of B. subtilis and S. aureus cells toward sublancin 168 was shown to depend on the presence of the large mechanosensitive channel of conductance MscL. In contrast, MscL was not involved in susceptibility toward the bacteriocin nisin or Pep5. Taken together, our unprecedented results demonstrate that MscL is a critical and specific determinant in bacterial sublancin 168 susceptibility that may serve either as a direct target for this lantibiotic or as a gate of entry to the cytoplasm.