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Brucella abortus siderophore 2,3-dihydroxybenzoic acid (DHBA) facilitates intracellular survival of the bacteria

机译:流产布鲁氏菌铁载体2,3-二羟基苯甲酸(DHBA)促进细菌的细胞内存活

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摘要

Siderophores are low molecular weight molecules that allow bacteria to acquire iron from host cell proteins. 2,3-dihydroxybenzoic acid (DHBA) is the only known siderophore produced by the intracellular pathogen Brucella abortus. Here its role in virulence was assessed by evaluating the ability of a mutant with a disruption of the entC gene to survive and replicate in vitro in murine and bovine cells and in vivo in resistant and susceptible murine hosts. It was hypothesized that DHBA is vital for bacterial virulence by its ability to chelate intracellular iron thereby preventing generation of anti-bacterial hydroxyl radicals via the Haber-Weiss reaction, to scavenge reactive oxygen intermediates and for acquisition of iron needed for nutritional purposes. The data showed DHBA played a significant role for bacterial survival in host cells after infection including in murine macrophages cultured in the presence and absence of exogenous interferon-gamma (IFN-gamma) and in bovine trophoblasts supplemented with erythritol. In severely iron-depleted conditions, DHBA was also found to be essential for growth in murine macrophages. Despite these deficiencies, the absence of DHBA had no long-term significant effect on the number of CFU recovered in vivo from either the Brucella-resistant C57BL/6 mice or Brucella-susceptible IFN-gamma knock-out C57BL/6 mice.
机译:铁载体是低分子量分子,可使细菌从宿主细胞蛋白中获取铁。 2,3-二羟基苯甲酸(DHBA)是细胞内病原体流产布鲁氏菌所产生的唯一已知铁载体。在这里,通过评估具有entC基因破坏的突变体在鼠和牛细胞中体外存活以及在抗性和易感鼠宿主中体内存活和复制的能力,来评估其在毒力中的作用。据推测,DHBA通过螯合细胞内铁从而防止通过Haber-Weiss反应产生抗菌羟基自由基,清除活性氧中间体以及获得营养所需的铁而对细菌的致病力至关重要。数据显示,DHBA对于感染后宿主细胞中的细菌存活具有重要作用,包括在存在和不存在外源干扰素-γ(IFN-γ)的条件下培养的鼠巨噬细胞以及补充赤藓糖醇的牛滋养细胞中。在严重缺铁的条件下,还发现DHBA对鼠巨噬细胞的生长至关重要。尽管存在这些不足,但DHBA的缺乏对从布鲁氏菌抗性C57BL / 6小鼠或布鲁氏菌敏感的IFN-γ敲除C57BL / 6小鼠体内回收的CFU数量没有长期的显着影响。

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