Multiple transporters are involved in natamycin efflux in Streptomyces chattanoogensis L10
Multiple transporters are involved in natamycin efflux in Streptomyces chattanoogensis L10
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DOI：
10.1111/mmi.13583
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发表时间：
2017-02
影响因子：
3.6
通讯作者：
Tanjun Wang;Y. Shan;Han Li;Weiwang Dou;Xin-Hang Jiang;X. Mao;Shui-Ping Liu;W. Guan;Yong-Quan Li
中科院分区：
文献类型：
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作者：
Tanjun Wang;Y. Shan;Han Li;Weiwang Dou;Xin-Hang Jiang;X. Mao;Shui-Ping Liu;W. Guan;Yong-Quan Li
产生抗生素的微生物已经进化出几种自我抗性机制来防止自身毒性。过量表达特异性转运蛋白以提高有毒抗生素的外排已被发现是许多链霉菌菌株使用的最重要和内在的抗性策略之一。在这项工作中，两个ATP结合盒（ABC）转运蛋白编码基因位于纳他霉素生物合成基因簇，scnA和scnB，被确定为在链霉菌chattanoogensis L10中纳他霉素外排的主要输出基因。另外两个位于集群外的转运蛋白，一个主要的促进超家族转运蛋白Mfs 1和ABC转运蛋白NepI/II被发现在纳他霉素外排中发挥互补作用。ScnA/ScnB和Mfs 1还参与输出纳他霉素的直接前体4，5-去环氧纳他霉素，其对S. chattanoogensis L10的活性高于纳他霉素。作为游霉素外排的主要互补输出者，Mfs 1响应于游霉素和4，5-去环氧游霉素的细胞内积累而上调，表明在自我抗性的应激反应中起关键作用。本文讨论了链霉菌中一种新的抗生素相关的外排和反应系统，以及抗生素生产菌株的自我耐药机制。
Antibiotic‐producing microorganisms have evolved several self‐resistance mechanisms to prevent auto‐toxicity. Overexpression of specific transporters to improve the efflux of toxic antibiotics has been found one of the most important and intrinsic resistance strategies used by many Streptomyces strains. In this work, two ATP‐binding cassette (ABC) transporter‐encoding genes located in the natamycin biosynthetic gene cluster, scnA and scnB, were identified as the primary exporter genes for natamycin efflux in Streptomyces chattanoogensis L10. Two other transporters located outside the cluster, a major facilitator superfamily transporter Mfs1 and an ABC transporter NepI/II were found to play a complementary role in natamycin efflux. ScnA/ScnB and Mfs1 also participate in exporting the immediate precursor of natamycin, 4,5‐de‐epoxynatamycin, which is more toxic to S. chattanoogensis L10 than natamycin. As the major complementary exporter for natamycin efflux, Mfs1 is up‐regulated in response to intracellular accumulation of natamycin and 4,5‐de‐epoxynatamycin, suggesting a key role in the stress response for self‐resistance. This article discusses a novel antibiotic‐related efflux and response system in Streptomyces, as well as a self‐resistance mechanism in antibiotic‐producing strains.