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硝酸镓对多黏菌素耐药肺炎克雷伯菌的抗菌活性。

Antibacterial activity of gallium nitrate against polymyxin-resistant Klebsiella pneumoniae strains.

机构信息

Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados - UFGD, Dourados, Mato Grosso do Sul, Brazil.

Laboratório de Pesquisa em Ciências da Saúde, Universidade Federal da Grande Dourados - UFGD, Dourados, Mato Grosso do Sul, Brazil.

出版信息

Diagn Microbiol Infect Dis. 2022 Feb;102(2):115569. doi: 10.1016/j.diagmicrobio.2021.115569. Epub 2021 Oct 8.

DOI:10.1016/j.diagmicrobio.2021.115569
PMID:34775292
Abstract

Iron uptake and metabolism have become attractive targets for the development of new antibacterial drugs. In this scenario, the FDA-approved iron mimetic metal gallium [Ga (III)] has been successfully researched as an antimicrobial drug. Ga (III) inhibits microbial growth by disrupting ferric iron-dependent metabolic pathways. In this study, we revealed that gallium nitrate III (GaN) inhibits the growth of a collection of twenty polymyxin-resistant Klebsiella pneumoniae strains at concentrations ranging from 2 to 16µg/mL, using a medium, on which the low iron content and the presence of human serum better mimic the in vivo environment. GaN was also successful in protecting Caenorhabditis elegans from polymyxin-resistant K. pneumoniae strains lethal infection, with survival rates of >75%. GaN also exhibited synergism with polymyxin B, suggesting that a polymyxin B-GaN combination holds promise like as one alternative therapy for infections caused by resistant polymyxin B K. pneumoniae strains.

摘要

铁的摄取和代谢已成为开发新型抗菌药物的有吸引力的靶点。在这种情况下,已被 FDA 批准的铁模拟金属镓[Ga(III)]已成功被研究为一种抗菌药物。Ga(III)通过破坏依赖三价铁的代谢途径来抑制微生物的生长。在这项研究中,我们发现硝酸镓 III(GaN)在一种培养基中,在 2 至 16μg/mL 的浓度范围内抑制了二十株多粘菌素耐药肺炎克雷伯菌菌株的生长,在这种培养基中,低铁含量和人血清的存在更好地模拟了体内环境。GaN 还成功地保护秀丽隐杆线虫免受多粘菌素耐药肺炎克雷伯菌菌株的致死性感染,存活率>75%。GaN 与多粘菌素 B 也表现出协同作用,这表明多粘菌素 B-GaN 联合具有作为治疗多粘菌素 B 耐药肺炎克雷伯菌菌株引起的感染的替代疗法的潜力。

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