Gallium induces the production of virulence factors in Pseudomonas aeruginosa
Gallium induces the production of virulence factors in Pseudomonas aeruginosa
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DOI：
10.1111/2049-632x.12105
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发表时间：
2014-02-01
影响因子：
3.3
通讯作者：
Wood, Thomas K.
中科院分区：
文献类型：
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作者：
Garcia-Contreras, Rodolfo;Perez-Eretza, Berenice;Wood, Thomas K.
新型抗菌药物镓是一种非氧化还原铁III类似物，具有抑菌和杀菌特性，对铜绿假单胞菌感染小鼠和家兔模型的体内和体外治疗均有效。它干扰铁的代谢、运输，并可能干扰铁的体内平衡。由于镓通过与铁竞争发挥其抗菌作用，我们假设它最终会导致细胞缺铁状态。由于铁缺乏在体外促进毒力因子的表达，并在动物模型中促进铜绿假单胞菌的致病性，预计镓治疗也会促进毒力因子的产生。为了验证这一假设，我们将参考菌株PA14和两株囊性纤维化患者的临床分离菌株暴露于镓中，并测定了它们的pyocyanin、鼠李糖脂、弹性酶、碱性蛋白酶、海藻酸盐、pyoverdine和生物膜的产量。除吡咯代碱外，镓处理对三株菌株的毒力因子均有诱导作用。此外，由于Ga诱导的毒力因子受群体感应控制，我们对Ga和群体猝灭剂溴化呋喃酮C-30共同施用进行了研究，发现C-30减轻了镓对其生长的抑制作用。因此，同时添加C-30和镓可能对铜绿假单胞菌感染的治疗更有效。
The novel antimicrobial gallium is a nonredox iron III analogue with bacteriostatic and bactericidal properties, effective for the treatment of Pseudomonas aeruginosa in vitro and in vivo in mouse and rabbit infection models. It interferes with iron metabolism, transport, and presumably its homeostasis. As gallium exerts its antimicrobial effects by competing with iron, we hypothesized that it ultimately will lead cells to an iron deficiency status. As iron deficiency promotes the expression of virulence factors in vitro and promotes the pathogenicity of P.aeruginosa in animal models, it is anticipated that treatment with gallium will also promote the production of virulence factors. To test this hypothesis, the reference strain PA14 and two clinical isolates from patients with cystic fibrosis were exposed to gallium, and their production of pyocyanin, rhamnolipids, elastase, alkaline protease, alginate, pyoverdine, and biofilm was determined. Gallium treatment induced the production of all the virulence factors tested in the three strains except for pyoverdine. In addition, as the Ga-induced virulence factors are quorum sensing controlled, co-administration of Ga and the quorum quencher brominated furanone C-30 was assayed, and it was found that C-30 alleviated growth inhibition from gallium. Hence, adding both C-30 and gallium may be more effective in the treatment of P.aeruginosa infections.