REPRESSOR MUTATIONS IN THE MARRAB OPERON THAT ACTIVATE OXIDATIVE STRESS GENES AND MULTIPLE ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI
REPRESSOR MUTATIONS IN THE MARRAB OPERON THAT ACTIVATE OXIDATIVE STRESS GENES AND MULTIPLE ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI
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DOI：
10.1128/jb.176.1.143-148.1994
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发表时间：
1994-01-01
影响因子：
3.2
通讯作者：
DEMPLE, B
中科院分区：
文献类型：
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作者：
ARIZA, RR;COHEN, SP;DEMPLE, B
对多种抗生素和某些氧化应激化合物的抗性是由三个独立选择的突变（marR 1，soQ 1和cfxB 1）赋予的，这些突变定位于大肠杆菌染色体上的34分钟。该位点的突变可激活marRAB操纵子，其中马尔R编码推定的mar转录阻遏物，而marA编码推定的抗抗生素和氧化剂防御基因的转录激活物。野生型马尔R蛋白的过表达逆转了所有三种突变体的表型（抗生素抗性和抗氧化酶合成增加）。DNA序列分析表明，与marR 1一样，另外两个突变是马尔R的改变：cfxB 1的285-bp缺失和soxQ 1的第70位密码子的GC->AT转换（Ala->Thr）。所有三种突变都导致mar特异性RNA的量增加，这支持了马尔R在marRAB操纵子表达中具有阻遏物功能的假设。在marR 1和soxQ 1菌株中，四环素进一步诱导mar RNA水平，但在cfxB 1缺失突变体中不诱导。在cfxB 1菌株中，无论是否暴露于四环素，截短RNA的表达水平与其他两种突变体中完全诱导的水平相同。cfxB 1菌株中过量产生的马尔R抑制了截短RNA的转录，并恢复了四环素的转录诱导。因此，marRAB操纵子的诱导是由马尔R所施加的抑制的缓解引起的。marRAB操纵子明显激活抗生素抗性和氧化应激基因。
Resistance to multiple antibiotics and certain oxidative stress compounds was conferred by three independently selected mutations (marR1, soQ1, and cfxB1) that mapped to 34 min on the Escherichia coli chromosome. Mutations at this locus can activate the marRAB operon, in which marR encodes a putative repressor of mar transcription and marA encodes a putative transcriptional activator of defense genes against antibiotics and oxidants. Overexpression of the wild-type MarR protein reversed the phenotypes (antibiotic resistance and increased antioxidant enzyme synthesis) of all three mutants. DNA sequence analysis showed that, like marR1, the other two mutations were alterations of marR: a 285-bp deletion in cfxB1 and a GC-->AT transition at codon 70 (Ala-->Thr) in soxQ1. All three mutations cause increased amounts of mar-specific RNA, which supports the hypothesis that MarR has a repressor function in the expression of the marRAB operon. The level of mar RNA was further induced by tetracycline in both the marR1 and soxQ1 strains but not in the cfxB1 deletion mutant. In the cfxB1 strain, the level of expression of a truncated RNA, with or without tetracycline exposure, was the same as the fully induced level in the other two mutants. Overproduction of MarR in the cfxB1 strain repressed the transcription of the truncated RNA and restored transcriptional inducibility by tetracycline. Thus, induction of the marRAB operon results from the relief of the repression exerted by MarR. The marRAB operon evidently activates both antibiotic resistance and oxidative stress genes.