A BACTERIAL ANALOG OF THE MDR GENE OF MAMMALIAN TUMOR-CELLS IS PRESENT IN STREPTOMYCES-PEUCETIUS, THE PRODUCER OF DAUNORUBICIN AND DOXORUBICIN
A BACTERIAL ANALOG OF THE MDR GENE OF MAMMALIAN TUMOR-CELLS IS PRESENT IN STREPTOMYCES-PEUCETIUS, THE PRODUCER OF DAUNORUBICIN AND DOXORUBICIN
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DOI：
10.1073/pnas.88.19.8553
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发表时间：
1991-10-01
影响因子：
11.1
通讯作者：
HUTCHINSON, CR
中科院分区：
文献类型：
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作者：
GUILFOILE, PG;HUTCHINSON, CR
对peucetius Streptomyces （American Type Culture Collection 29050）的drrAB基因座进行序列分析，发现其存在drrA和drrB两个基因，这两个基因都是异源宿主Streptomyces lividans对柔红霉素和阿霉素耐药所必需的。DrrA蛋白类似于一个atp结合转运蛋白大家族，包括由哺乳动物肿瘤细胞的mdr基因编码的蛋白，这些蛋白赋予对柔红霉素、阿霉素和其他一些结构无关的化疗药物的耐药性。DrrB蛋白与其他已知蛋白没有明显的相似性，但可能是非常疏水的，这表明它位于细菌膜中。这两种蛋白可能通过类似于为含有扩增或过表达mdr基因的哺乳动物肿瘤细胞建立的抗转运机制，共同作用赋予柔红霉素和阿霉素耐药性。drrAB区域的转录分析支持含有drrA和drrB的一个转录本的存在，并表明这些基因仅在抗生素生产过程中表达。
Sequence analysis of the drrAB locus from Streptomyces peucetius (American Type Culture Collection 29050) reveals the presence of two genes, drrA and drrB, both of which are required for daunorubicin and doxorubicin (Adriamycin) resistance in the heterologous host Streptomyces lividans. The DrrA protein is similar to a large family of ATP-binding transport proteins, including the proteins encoded by the mdr genes from mammalian tumor cells, which confer resistance to daunorubicin, doxorubicin, and some other structurally unrelated chemotherapeutic agents. The DrrB protein shows no significant similarity to other known proteins but is probably very hydrophobic, suggesting that it is located in the bacterial membrane. These two proteins may act jointly to confer daunorubicin and doxorubicin resistance by an analog of the antiport mechanism established for mammalian tumor cells that contain amplified or overexpressed mdr genes. Transcriptional analysis of the drrAB region supports the presence of one transcript containing drrA and drrB and indicates that these genes are expressed only during antibiotic production.