Microbiome-derived antimicrobial peptides show therapeutic activity against the critically important priority pathogen, Acinetobacter baumannii.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY npj Biofilms and Microbiomes Pub Date : 2024-09-30 DOI:10.1038/s41522-024-00560-2

P J Alexander, L B Oyama, H Olleik, F Godoy Santos, S O'Brien, A Cookson, S A Cochrane, B F Gilmore, M Maresca, S A Huws

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Abstract

Acinetobacter baumannii is designated by the World Health Organisation as a critical priority pathogen. Previously we discovered antimicrobial peptides (AMPs), namely Lynronne-1, -2 and -3, with efficacy against bacterial pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. Here we assessed Lynronne-1, -2 and -3 structure by circular dichroism and efficacy against clinical strains of A. baumannii. All Lynronne AMPs demonstrated alpha-helical secondary structures and had antimicrobial activity towards all tested strains of A. baumannii (Minimum Inhibitory Concentrations 2-128 μg/ml), whilst also having anti-biofilm activity. Lynronne-2 and -3 demonstrated additive effects with amoxicillin and erythromycin, and synergy with gentamicin. The AMPs demonstrated little toxicity towards mammalian cell lines or Galleria mellonella. Fluorescence-based assay data demonstrated that Lynronne-1 and -3 had higher membrane-destabilising action against A. baumannii in comparison with Lynronne-2, which was corroborated by transcriptomic analysis. For the first time, we demonstrate the therapeutic activity of Lynronne AMPs against A. baumannii.

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微生物衍生的抗菌肽对极为重要的重点病原体鲍曼不动杆菌具有治疗活性。

鲍曼不动杆菌被世界卫生组织指定为重要的优先病原体。在此之前，我们发现了抗菌肽（AMPs），即 Lynronne-1、-2 和 -3，它们对金黄色葡萄球菌和铜绿假单胞菌等细菌病原体具有疗效。在这里，我们通过圆二色性评估了 Lynronne-1、-2 和 -3 的结构以及对鲍曼尼杆菌临床菌株的疗效。所有 Lynronne AMP 均显示出α-螺旋二级结构，对所有测试的鲍曼不动杆菌菌株均具有抗菌活性（最低抑菌浓度为 2-128 μg/ml），同时还具有抗生物膜活性。Lynronne-2和-3与阿莫西林和红霉素具有相加作用，与庆大霉素具有协同作用。这两种 AMP 对哺乳动物细胞系或鼠瘿蚊的毒性很小。基于荧光的检测数据表明，与 Lynronne-2 相比，Lynronne-1 和 Lynronne-3 对鲍曼不动杆菌具有更强的膜破坏作用，转录组分析也证实了这一点。我们首次证明了 Lynronne AMPs 对鲍曼尼氏菌的治疗活性。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.