Center for Integrated Protein Science Munich, Department Chemie, Technische Universität München, 85747 Garching, Germany.
Proc Natl Acad Sci U S A. 2013 Jun 4;110(23):9493-8. doi: 10.1073/pnas.1300578110. Epub 2013 May 20.
Oxidant-mediated antibacterial response systems are broadly used to control bacterial proliferation. Hypochlorite (HOCl) is an important component of the innate immune system produced in neutrophils and specific epithelia. Its antimicrobial activity is due to damaging cellular macromolecules. Little is known about how bacteria escape HOCl-inflicted damage. Recently, the transcription factor YjiE was identified that specifically protects Escherichia coli from HOCl killing. According to its function, YjiE is now renamed HypT (hypochlorite-responsive transcription factor). Here we unravel that HypT is activated by methionine oxidation to methionine sulfoxide. Interestingly, so far only inactivation of cellular proteins by methionine oxidation has been reported. Mutational analysis revealed three methionines that are essential to confer HOCl resistance. Their simultaneous substitution by glutamine, mimicking the methionine sulfoxide state, increased the viability of E. coli cells upon HOCl stress. Triple glutamine substitution generates a constitutively active HypT that regulates target genes independently of HOCl stress and permanently down-regulates intracellular iron levels. Inactivation of HypT depends on the methionine sulfoxide reductases A/B. Thus, microbial protection mechanisms have evolved along the evolution of antimicrobial control systems, allowing bacteria to survive within the host environment.
氧化剂介导的抗菌反应系统被广泛用于控制细菌增殖。次氯酸（HOCl）是中性粒细胞和特定上皮细胞产生的固有免疫系统的重要组成部分。其抗菌活性归因于破坏细胞大分子。关于细菌如何逃避次氯酸造成的损伤知之甚少。最近，鉴定出转录因子 YjiE，它特异性地保护大肠杆菌免受次氯酸的杀伤。根据其功能，YjiE 现在更名为 HypT（次氯酸反应转录因子）。在这里，我们揭示 HypT 被蛋氨酸氧化为蛋氨酸亚砜激活。有趣的是，到目前为止，仅报道了细胞蛋白的失活是通过蛋氨酸氧化实现的。突变分析显示了三个对赋予 HOCl 抗性至关重要的蛋氨酸。它们同时被谷氨酰胺取代，模拟蛋氨酸亚砜状态，增加了 E. coli 细胞在 HOCl 应激下的存活率。三谷氨酸取代产生了一种组成型激活的 HypT，它独立于 HOCl 应激调节靶基因，并永久下调细胞内铁水平。HypT 的失活依赖于蛋氨酸亚砜还原酶 A/B。因此，微生物保护机制沿着抗菌控制系统的进化而进化，使细菌能够在宿主环境中生存。
