Miller P F, Gambino L F, Sulavik M C, Gracheck S J
Therapeutics Department, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, Michigan 48106-1047.
Antimicrob Agents Chemother. 1994 Aug;38(8):1773-9. doi: 10.1128/AAC.38.8.1773.
Multiple antibiotic resistance in Escherichia coli has typically been associated with mutations at the mar locus, located at 34 min on the E. coli chromosome. A new mutant, marC, isolated on the basis of a Mar phenotype but which maps to the soxRS (encoding the regulators of the superoxide stress response) locus located at 92 min, is described here. This mutant shares several features with a known constitutive allele of the soxRS gene, prompting the conclusion that it is a highly active allele of this gene. The marC mutation has thus been given the designation soxR201. This new mutant was used to examine the relationship between the mar and sox loci in promoting antibiotic resistance. The results of these studies indicate that full antibiotic resistance resulting from the soxR201 mutation is partially dependent on an intact mar locus and is associated with an increase in the steady-state level of mar-specific mRNA. In addition, paraquat treatment of wild-type cells is shown to increase the level of antibiotic resistance in a dose-dependent manner that requires an intact soxRS locus. Conversely, overexpression of MarA from a multicopy plasmid results in weak activation of a superoxide stress response target gene. These findings are consistent with a model in which the regulatory factors encoded by the marA and soxS genes control the expression of overlapping sets of target genes, with MarA preferentially acting on targets involved with antibiotic resistance and SoxS directed primarily towards components of the superoxide stress response. Furthermore, compounds frequently used to induce the superoxide stress response, including paraquat, menadione, and phenazine methosulfate, differ with respect to the amount of protection provided against them by the antibiotic resistance response.
大肠杆菌中的多重抗生素耐药性通常与位于大肠杆菌染色体34分钟处的mar位点的突变有关。本文描述了一种新的突变体marC，它是根据Mar表型分离出来的，但定位在位于92分钟处的soxRS（编码超氧化物应激反应调节因子）位点。该突变体与soxRS基因的一个已知组成型等位基因具有几个共同特征，从而得出它是该基因的一个高活性等位基因的结论。因此，marC突变被命名为soxR201。这个新的突变体被用来研究mar和sox位点在促进抗生素耐药性方面的关系。这些研究结果表明，由soxR201突变产生的完全抗生素耐药性部分依赖于完整的mar位点，并且与mar特异性mRNA的稳态水平增加有关。此外，百草枯处理野生型细胞显示以剂量依赖的方式增加抗生素耐药性水平，这需要完整的soxRS位点。相反，从多拷贝质粒中过表达MarA会导致超氧化物应激反应靶基因的弱激活。这些发现与一个模型一致，即marA和soxS基因编码的调节因子控制重叠的靶基因集的表达，MarA优先作用于与抗生素耐药性有关的靶标，而SoxS主要针对超氧化物应激反应的成分。此外，常用于诱导超氧化物应激反应的化合物，包括百草枯、甲萘醌和吩嗪硫酸甲酯，在抗生素耐药反应提供的保护量方面存在差异。
