When subcloned into low-copy-number expression vectors, rumAB, encoding polV_R391 (RumA′₂B), is best characterized as a potent mutator giving rise to high levels of spontaneous mutagenesis in vivo. This is in dramatic contrast to the poorly mutable phenotype when polV_R391 is expressed from the native 88.5 kb R391, suggesting that R391 expresses cis-acting factors that suppress the expression and/or the activity of polV_R391. Indeed, we recently discovered that SetR_R391, an ortholog of λ cI repressor, is a transcriptional repressor of rumAB. Here, we report that CroS_R391, an ortholog of λ Cro, also serves as a potent transcriptional repressor of rumAB. Levels of RumA are dependent upon an interplay between SetR_R391 and CroS_R391, with the greatest reduction of RumA protein levels observed in the absence of SetR_R391 and the presence of CroS_R391. Under these conditions, CroS_R391 completely abolishes the high levels of mutagenesis promoted by polV_R391 expressed from low-copy-number plasmids. Furthermore, deletion of croS_R391 on the native R391 results in a dramatic increase in mutagenesis, indicating that CroS_R391 plays a major role in suppressing polV_R391 mutagenesis in vivo. Inactivating mutations in CroS_R391 therefore have the distinct possibility of increasing cellular mutagenesis that could lead to the evolution of antibiotic resistance of pathogenic bacteria harboring R391.

中文翻译：

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CroSR391 是 λ Cro 阻遏蛋白的直系同源物，在抑制 polVR391 依赖性诱变中发挥着重要作用

当亚克隆到低拷贝数表达载体中时，编码 polV _R391 (RumA' _{2 B) 的}rumAB被最好地表征为一种有效的突变子，在体内产生高水平的自发诱变。这与当polV _R391从天然88.5kb R391表达时的弱可变表型形成鲜明对比，表明R391表达抑制polV _R391的表达和/或活性的顺式作用因子。事实上，我们最近发现 SetR _R391是 λ cI 阻遏蛋白的直系同源物，也是rumAB的转录阻遏蛋白。在这里，我们报告 CroS _R391是 λ Cro 的直系同源物，也可作为rumAB的有效转录抑制因子。RumA 的水平取决于 SetR _R391和 CroS _{R391之间的相互作用，在 SetR R391不存在和 CroS R391}存在的情况下观察到 RumA 蛋白水平的最大降低。在这些条件下，CroS _R391完全消除了低拷贝数质粒表达的polV _R391所促进的高水平诱变。此外，在天然R391上删除croS _R391会导致诱变急剧增加，表明CroS _R391在体内抑制polV _R391诱变中发挥重要作用。因此， CroS _R391的失活突变很可能会增加细胞突变，从而导致携带 R391 的病原菌产生抗生素耐药性。