Guilfoile P G, Hutchinson C R
School of Pharmacy, University of Wisconsin, Madison 53706.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8553-7. doi: 10.1073/pnas.88.19.8553.
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.
对产自波赛链霉菌(美国模式培养物集存库29050)的drrAB基因座进行序列分析,发现存在两个基因,drrA和drrB,这两个基因对于在异源宿主天蓝色链霉菌中产生对柔红霉素和阿霉素(阿霉素)的抗性都是必需的。DrrA蛋白与一大类ATP结合转运蛋白相似,包括哺乳动物肿瘤细胞中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不相关的化疗药物的抗性。DrrB蛋白与其他已知蛋白没有明显相似性,但可能具有很强的疏水性,这表明它位于细菌膜中。这两种蛋白可能通过与含有扩增或过表达mdr基因的哺乳动物肿瘤细胞所建立的反向转运机制类似的方式共同作用,赋予对柔红霉素和阿霉素的抗性。对drrAB区域的转录分析支持存在一个包含drrA和drrB的转录本,并表明这些基因仅在抗生素产生期间表达。