Department of Biology, SSPC Pharma Research Centre, Maynooth University, Maynooth, Co Kildare, Ireland.
Department of Chemistry, SSPC Pharma Research Centre, RCSI, 123 St. Stephens Green, Dublin 2, Ireland.
J Biol Inorg Chem. 2020 Dec;25(8):1153-1165. doi: 10.1007/s00775-020-01831-x. Epub 2020 Oct 30.
Gallium-based drugs have been repurposed as antibacterial therapeutic candidates and have shown significant potential as an alternative treatment option against drug resistant pathogens. The activity of gallium (Ga) is a result of its chemical similarity to ferric iron (Fe) and substitution into iron-dependent pathways. Ga is redox inactive in typical physiological environments and therefore perturbs iron metabolism vital for bacterial growth. Gallium maltolate (GaM) is a well-known water-soluble formulation of gallium, consisting of a central gallium cation coordinated to three maltolate ligands, [Ga(Maltol)]. This study implemented a label-free quantitative proteomic approach to observe the effect of GaM on the bacterial pathogen, Pseudomonas aeruginosa. The replacement of iron for gallium mimics an iron-limitation response, as shown by increased abundance of proteins associated with iron acquisition and storage. A decreased abundance of proteins associated with quorum-sensing and swarming motility was also identified. These processes are a fundamental component of bacterial virulence and dissemination and hence suggest a potential role for GaM in the treatment of P. aeruginosa infection.
镓基药物已被重新用于抗菌治疗候选药物，作为一种针对耐药病原体的替代治疗选择，显示出巨大的潜力。镓 (Ga) 的活性是由于其与三价铁 (Fe) 的化学相似性，并取代了铁依赖性途径。在典型的生理环境中，Ga 的氧化还原活性为零，因此会破坏细菌生长所必需的铁代谢。镓麦芽糖酸盐 (GaM) 是一种众所周知的水溶性镓制剂，由一个中心镓阳离子与三个麦芽糖酸盐配体配位组成，[Ga（麦芽糖酸盐）]。本研究采用无标记定量蛋白质组学方法观察 GaM 对细菌病原体铜绿假单胞菌的影响。Ga 取代铁会模拟铁限制反应，如与铁摄取和储存相关的蛋白质丰度增加所示。还鉴定到与群体感应和群集运动相关的蛋白质丰度降低。这些过程是细菌毒力和传播的基本组成部分，因此表明 GaM 在治疗铜绿假单胞菌感染方面具有潜在作用。
