Department of Science, Roma Tre University, 00146 Rome, Italy.
Santa Lucia Fundation IRCCS, 00179 Rome, Italy.
ACS Infect Dis. 2022 Jan 14;8(1):78-85. doi: 10.1021/acsinfecdis.1c00409. Epub 2021 Dec 29.
The decreasing efficacy of existing antibiotics against pulmonary pathogens that affect cystic fibrosis (CF) patients calls for the development of novel antimicrobials. Iron uptake and metabolism are vital processes for bacteria, hence potential therapeutic targets. Gallium [Ga(III)] is a ferric iron-mimetic that inhibits bacterial growth by disrupting iron uptake and metabolism. In this work we evaluate the efficacy of three Ga(III) compounds, namely, Ga(NO), (GaN), Ga(III)-maltolate (GaM), and Ga(III)-protoporphyrin IX (GaPPIX), against a collection of CF pathogens using both reference media and media mimicking biological fluids. All CF pathogens, except , were susceptible to at least one Ga(III) compound. Notably, and were susceptible to all Ga(III) compounds. , complex, and were more susceptible to GaN and GaM, whereas and were more sensitive to GaPPIX. The results of this study support the development of Ga(III)-based therapy as a broad-spectrum strategy to treat CF lung infections.
现有的抗生素对影响囊性纤维化 (CF) 患者的肺部病原体的疗效下降，因此需要开发新的抗菌药物。铁的摄取和代谢是细菌的重要过程，因此是潜在的治疗靶点。镓[Ga(III)]是一种铁模拟物，通过破坏铁的摄取和代谢来抑制细菌生长。在这项工作中，我们使用参考培养基和模拟生物液的培养基评估了三种 Ga(III)化合物，即 Ga(NO₃)、GaN、Ga(III)-酒石酸盐 (GaM) 和 Ga(III)-原卟啉 IX (GaPPIX)，对一系列 CF 病原体的疗效。除 外，所有 CF 病原体对至少一种 Ga(III)化合物敏感。值得注意的是，所有 Ga(III)化合物对 和 都敏感。 、 复合物和 对 GaN 和 GaM 更敏感，而 和 对 GaPPIX 更敏感。这项研究的结果支持基于 Ga(III)的治疗作为治疗 CF 肺部感染的广谱策略的发展。
