The fungicidal activity of amphotericin B requires autophagy-dependent targeting to the vacuole under a nutrient-starved condition in Saccharomyces cerevisiae
The fungicidal activity of amphotericin B requires autophagy-dependent targeting to the vacuole under a nutrient-starved condition in Saccharomyces cerevisiae
复制标题
两性霉素 B 的杀菌活性需要在酿酒酵母营养匮乏的条件下以自噬依赖性靶向液泡
DOI：
10.1099/mic.0.000269
复制
发表时间：
2016
期刊：
影响因子：
1.5
通讯作者：
Tanaka T.
中科院分区：
文献类型：
--
作者：
Yoshioka M;Yamada K;Yamaguchi Y;Ogita A;Fujita KI;Tanaka T.
在这项研究中，我们证明，在蒸馏水，营养饥饿的条件下，eliminated自噬在酿酒酵母，一系列的自噬缺陷突变体是耐真菌素B的杀菌作用。此外，我们发现，丹磺酰标记的衍生物的抗生素共定位与解体空泡在整个细胞质中悬浮在蒸馏水中的阿氏菌素B敏感的亲本菌株。相比之下，丹磺酰标记的衍生物在Δ atg18菌株中没有内化，Δ atg18菌株缺乏自噬体的形成，这是自噬的关键早期步骤。然而，该衍生物在Δ vma 1突变体的结构完整的液泡中积累，没有显着毒性，该突变体缺乏自噬体（自噬的最后阶段）的降解。我们的数据支持这样的想法，即阿替霉素B可以利用自噬依赖性运输到液泡内腔中，在那里它与膜的腔叶相互作用，导致结构上的灾难性影响。
In this study, we demonstrated that in distilled water, a nutrient-starved condition that elicits autophagy inSaccharomyces cerevisiae, an array of autophagy-deficient mutants are resistant to the fungicidal effects of amphotericin B. In addition, we found that a dansyl-labelled derivative of the antibiotic colocalized with disintegrated vacuoles throughout the cytoplasm in the amphotericin B-sensitive parental strain suspended in distilled water. In contrast, the dansyl-labelled derivative was not internalized in the Δatg18strain, which is deficient in the formation of autophagosomes, a key early step in autophagy. However, the derivative accumulated without significant toxicity in structurally intact vacuoles in the Δvma1mutant, which is deficient in the degradation of autophagic bodies, the final stage in autophagy. Our data support the idea that amphotericin B can utilize autophagy-dependent trafficking into the intra-vacuolar lumen, where it interacts with the luminal leaf of the membrane to cause structurally catastrophic effects.