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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Linearmycins are lytic membrane-targeting antibiotics
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Linearmycins are lytic membrane-targeting antibiotics

机译：LineAlmycins是裂解膜靶向抗生素

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The linearmycin family of polyketides was originally classified as antifungal metabolites. However, in addition to antifungal activity, we previously found that linearmycins cause cellular lysis and colony degradation of the Gram-positive bacterium Bacillus subtilis. We recently showed that Streptomyces sp. strain Mg1 incorporates linearmycins into extracellular vesicles, which are capable of lysing B. subtilis. However, the mechanism of linearmycin-induced lysis was hitherto unexplored. Therefore, we sought to determine how linearmycin-laden vesicles cause lysis. In this study, we found that linearmycins inhibited the growth of all Gram-positive bacteria that we tested, but lysis was limited to some Bacillus species. Next, we found that linearmycin-induced lysis occurred even when cellular metabolism and growth were inhibited, which suggested that linearmycins possess the intrinsic capacity to lyse cells, unlike cell-wall targeting antibiotics. We showed that linearmycin exposure caused changes consistent with rapid depolarization of the B. subtilis cytoplasmic membrane, which was correlated with a loss of viability. Finally, using liposomes as in vitro membrane models, we demonstrated that linearmycins are capable of disrupting lipid bilayers without any other cellular components. Taken together, our results strongly indicate that the cytoplasmic membrane is the direct antibacterial target of linearmycins.
机译：最初被归类为抗真菌代谢物的LineAlmycin家族。然而，除了抗真菌活性之外，我们以前发现Linearmycins引起革兰氏阳性菌枯草芽孢杆菌的细胞裂解和殖民地降解。我们最近表明Streptomyces sp。菌株Mg1将线性霉素掺入细胞外囊泡，其能够裂解B.枯草芽孢杆菌。然而，LiNearmycin诱导的裂解机制迄今为止未探索。因此，我们试图确定Linearmycin-Laden囊泡的引起裂解。在这项研究中，我们发现LineAlmycins抑制了我们测试的所有革兰氏阳性细菌的生长，但裂解仅限于一些芽孢杆菌物种。接下来，我们发现即使当抑制细胞代谢和生长时，也发生了线性霉素诱导的裂解，这表明线性霉素具有莱耶细胞的内在能力，与靶向抗生素不同。我们表明，线性霉素暴露引起的变化与枯草芽孢杆菌细胞质膜的快速去极化相一致，这与活力损失相关。最后，使用脂质体作为体外膜模型，我们证明了线性霉素能够破坏脂质双层而没有任何其他细胞组分。在一起，我们的结果强烈表示细胞质膜是直接霉素的直接抗菌靶标。

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