The RecRO pathway of DNA recombinational repair in Helicobacter pylori and its role in bacterial survival in the host.

The RecRO pathway of DNA recombinational repair in Helicobacter pylori and its role in bacterial survival in the host.
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DOI:
10.1016/j.dnarep.2011.01.004
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发表时间:
2011-04-03
期刊:
影响因子:
3.8
通讯作者:
Maier RJ
Maier RJ
中科院分区:
医学3区
文献类型:
--
作者:
Wang G;Lo LF;Maier RJ

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在幽门螺杆菌(Helicobacter pylori)中鉴定了两种DNA重组途径,AddAB(RecBCD样)和RecRO,幽门螺杆菌是一种定植于人类胃中的致病细菌,导致一系列胃部疾病。在这项研究中,我们研究了H。pylori RecRO途径在DNA重组修复中的作用我们对H. pylori recR和recO中的单突变体、推定的缺口修复重组途径中的基因,以及因此在启动DNA重组修复的两种途径中都有缺陷的addA recO双突变体。recR或recO单突变体对丝裂霉素C的敏感性与亲本菌株相同,表明RecRO途径不负责DNA双链断裂的修复。然而,H. pylori recR和recO突变体对氧化应激和酸应激高度敏感,这是H. pylori在其生理生态位中遇到的问题。recR突变体的互补恢复了对氧化和酸胁迫的敏感性至野生型水平。通过测量DNA转化频率,recR和recO单突变体被证明对基因组间重组没有影响,而addA recO双突变体的转化频率大大降低(约12倍)。另一方面,RecRO途径显示在与直接重复序列的基因组内重组中起重要作用。而recA菌株的缺失频率比背景水平低35倍,recR的失活导致缺失频率降低4倍。在小鼠感染模型中,三种突变株在宿主胃中定植的能力大大降低。野生型、recR、recO和addA recO菌株的定殖数的几何平均值分别为6 × 105、1.6 × 104、1.4 × 104和4 × 103 CFU/g胃。H.因此,幽门螺杆菌RecRO介导的DNA重组修复(基因组内重组)参与修复由氧化和酸应激诱导的DNA损伤,并在宿主中细菌存活和持续定植中起重要作用。
Two pathways for DNA recombination, AddAB (RecBCD-like) and RecRO, were identified in Helicobacter pylori, a pathogenic bacterium that colonizes human stomachs resulting in a series of gastric diseases. In this study, we examined the physiological roles of H. pylori RecRO pathway in DNA recombinational repair. We characterized H. pylori single mutants in recR and in recO, genes in the putative gap repair recombination pathway, and an addA recO double mutant that is thus deficient in both pathways that initiate DNA recombinational repair. The recR or recO single mutants showed the same level of sensitivity to mitomycin C as the parent strain, suggesting that the RecRO pathway is not responsible for the repair of DNA double strand breaks. However, H. pylori recR and recO mutants are highly sensitive to oxidative stress and separately to acid stress, two major stress conditions that H. pylori encounters in its physiological niche. The complementation of the recR mutant restored the sensitivity to oxidative and acid stress to the wild type level. By measuring DNA transformation frequencies, the recR and recO single mutants were shown to have no effect on inter-genomic recombination, whereas the addA recO double mutant had a greatly (~12-fold) reduced transformation frequency. On the other hand, the RecRO pathway was shown to play a significant role in intra-genomic recombination with direct repeat sequences. Whereas the recA strain had a deletion frequency 35-fold lower than that of background level, inactivation of recR resulted in a 4-fold decrease in deletion frequency. In a mouse infection model, the three mutant strains displayed a greatly reduced ability to colonize the host stomachs. The geometric means of colonization number for the wild type, recR, recO, and addA recO strains were 6 × 105, 1.6 × 104, 1.4 × 104 and 4 × 103 CFU/g stomach, respectively. H. pylori RecRO-mediated DNA recombinational repair (intra-genomic recombination) is thus involved in repairing DNA damage induced by oxidative and acid stresses and plays an important role in bacterial survival and persistent colonization in the host.
DOI: 10.1038/35003501
发表时间: 2000-03-02
期刊: NATURE
影响因子: 64.8
作者:
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影响因子: 11.1
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发表时间: 2008-11-24
期刊: PLOS ONE
影响因子: 3.7
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DOI: 10.1111/j.1365-2958.1991.tb02084.x
发表时间: 1991-10-01
影响因子: 3.6
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