Wang Hui, Naseer Nawar, Chen Yaran, Zhu Anthony Y, Kuai Xuewen, Galagedera Nirupa, Liu Zhi, Zhu Jun
Department of Microbiology, Nanjing Agricultural University, Nanjing, China
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Infect Immun. 2017 Mar 23;85(4). doi: 10.1128/IAI.00929-16. Print 2017 Apr.
Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen , the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in , which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene , encoding an alkylhydroperoxide reductase, independently of HO A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either or rendered more resistant to HO RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in mutants even in the absence of HO Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of HO Furthermore, we showed that Δ and Δ mutants were less fit when anaerobically grown bacteria were exposed to low levels of HO or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the oxidative stress response.
细菌已发展出应对不同压力并适应不同环境生态位的能力。人类病原体霍乱弧菌是严重腹泻疾病霍乱的病原体，它利用转录调节因子OxyR来激活与抗氧化应激相关的基因，包括过氧化物还原酶PrxA，以应对过氧化氢。在本研究中，我们在霍乱弧菌中鉴定出另一个OxyR同源物，我们将其命名为OxyR2，并将之前的OxyR重新命名为OxyR1。我们发现，OxyR2需要独立于H₂O₂激活其反向转录的基因ahpC，该基因编码一种烷基过氧化氢还原酶。OxyR2中一个保守的半胱氨酸残基对该功能至关重要。ahpC或oxyR2的突变使霍乱弧菌对H₂O₂更具抗性。RNA测序分析表明，即使在没有H₂O₂的情况下，OxyR1激活的抗氧化应激基因在oxyR2突变体中也高度表达。进一步的遗传分析表明，OxyR2激活的AhpC通过维持细胞内低浓度的H₂O₂来调节OxyR1的活性。此外，我们表明，当厌氧生长的细菌暴露于低水平的H₂O₂或在海水中培养时，ΔoxyR2和ΔahpC突变体的适应性较差。这些结果表明，OxyR2和AhpC在霍乱弧菌的氧化应激反应中起重要作用。
