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首页> 外文期刊>Antimicrobial agents and chemotherapy. >The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source.
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The antibacterial activity of Ga3+ is influenced by ligand complexation as well as the bacterial carbon source.

机译:Ga3 +的抗菌活性受配体络合以及细菌碳源的影响。

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Gallium ions have previously been shown to exhibit antibacterial and antibiofilm properties. In this study, we report differential bactericidal activities of two gallium complexes, gallium desferrioxamine B (Ga-DFOB) and gallium citrate (Ga-Cit). Modeling of gallium speciation in growth medium showed that DFOB and citrate both can prevent precipitation of Ga(OH)(3), but some precipitation can occur above pH 7 with citrate. Despite this, Ga-Cit 90% inhibitory concentrations (IC(90)) were lower than those of Ga-DFOB for clinical isolates of Pseudomonas aeruginosa and several reference strains of other bacterial species. Treatment with Ga compounds mitigated damage inflicted on murine J774 macrophage-like cells infected with P. aeruginosa PAO1. Again, Ga-Cit showed more potent mitigation than did Ga-DFOB. Ga was also taken up more efficiently by P. aeruginosa in the form of Ga-Cit than in the form of Ga-DFOB. Neither Ga-Cit nor Ga-DFOB was toxic to several human cell lines tested, and no proinflammatory activity was detected in human lung epithelial cells after exposure in vitro. Metabolomic analysis was used to delineate the effects of Ga-Cit on the bacterial cell. Exposure to Ga resulted in lower concentrations of glutamate, a key metabolite for P. aeruginosa, and of many amino acids, indicating that Ga affects various biosynthesis pathways. An altered protein expression profile in the presence of Ga-Cit suggested that some compensatory mechanisms were activated in the bacterium. Furthermore, the antibacterial effect of Ga was shown to vary depending on the carbon source, which has importance in the context of medical applications of gallium.
机译:以前已经证明镓离子具有抗菌和抗生物膜特性。在这项研究中,我们报告了两种镓络合物,去铁胺B(Ga-DFOB)和柠檬酸镓(Ga-Cit)的不同杀菌活性。生长培养基中镓形态的模型表明,DFOB和柠檬酸盐均可阻止Ga(OH)(3)的沉淀,但在pH高于7的情况下,柠檬酸盐会发生一些沉淀。尽管如此,对于铜绿假单胞菌的临床分离株和其他细菌种类的几种参考菌株,Ga-Cit的90%抑制浓度(IC(90))低于Ga-DFOB。用Ga化合物处理可减轻铜绿假单胞菌PAO1感染对小鼠J774巨噬细胞样细胞造成的损害。再次,Ga-Cit显示出比Ga-DFOB更有效的缓解方法。铜绿假单胞菌还以Ga-Cit形式比Ga-DFOB形式更有效地吸收了Ga。 Ga-Cit和Ga-DFOB均未对几种测试的人类细胞系产生毒性,并且在体外暴露后在人类肺上皮细胞中未检测到促炎活性。用代谢组学分析来描述Ga-Cit对细菌细胞的作用。暴露于Ga会导致较低浓度的谷氨酸(铜绿假单胞菌的重要代谢产物)和许多氨基酸的浓度降低,表明Ga影响各种生物合成途径。在存在Ga-Cit的情况下改变的蛋白质表达谱表明该细菌中某些补偿机制被激活。此外,显示出Ga的抗菌作用根据碳源而变化,这在镓的医学应用中具有重要意义。

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