Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection.
Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection.
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DOI：
10.1038/srep30201
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发表时间：
2016-07-22
影响因子：
4.6
通讯作者：
Walker D
中科院分区：
文献类型：
--
作者：
McCaughey LC;Ritchie ND;Douce GR;Evans TJ;Walker D
蛋白质抗生素，被称为细菌素，广泛由细菌产生用于种内竞争。细菌素的效力和靶向作用表明，它们可以被开发成临床上有用的抗生素，以对抗几乎没有治疗选择的高度耐药的革兰氏阴性病原体。在这里，我们表明，铜绿假单胞菌特异性细菌素，被称为绿脓菌素，在铜绿假单胞菌肺部感染的小鼠模型中显示出强大的功效，其中提供保护免受致命感染所需的绿脓菌素S5的浓度至少比最常用的吸入抗生素妥布霉素低100倍。另外，绿脓菌素在肺中是稳定的，在高浓度下免疫原性差，并且在重复绿脓菌素施用后在绿脓菌素特异性抗体存在下维持功效。细菌素编码基因经常在微生物基因组中发现，因此可以随时提供针对有问题的革兰氏阴性病原体的高度靶向和有效的抗生素活性。
Protein antibiotics, known as bacteriocins, are widely produced by bacteria for intraspecies competition. The potency and targeted action of bacteriocins suggests that they could be developed into clinically useful antibiotics against highly drug resistant Gram-negative pathogens for which there are few therapeutic options. Here we show that Pseudomonas aeruginosa specific bacteriocins, known as pyocins, show strong efficacy in a murine model of P. aeruginosa lung infection, with the concentration of pyocin S5 required to afford protection from a lethal infection at least 100-fold lower than the most commonly used inhaled antibiotic tobramycin. Additionally, pyocins are stable in the lung, poorly immunogenic at high concentrations and efficacy is maintained in the presence of pyocin specific antibodies after repeated pyocin administration. Bacteriocin encoding genes are frequently found in microbial genomes and could therefore offer a ready supply of highly targeted and potent antibiotics active against problematic Gram-negative pathogens.