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两种对呼吸道耐甲氧西林金黄色葡萄球菌有活性的噬菌体的裂解活性、稳定性、生物膜破坏能力及基因组特征

Lytic activity, stability, biofilm disruption capabilities, and genomic characterization of two bacteriophages active against respiratory MRSA.

作者信息

Iszatt Joshua J, Larcombe Alexander N, Garratt Luke W, Stick Stephen M, Kicic Anthony

机构信息

Occupation, Environment and Safety, School of Population Health, Curtin University, Perth 6102, Australia.

Wal-yan Respiratory Research Centre, The Kids Research Institute Australia, Perth 6009, Australia.

出版信息

J Appl Microbiol. 2025 Apr 1;136(4). doi: 10.1093/jambio/lxaf081.

Abstract

AIMS

This study aimed to characterize bacteriophages for potential therapeutic use against Staphylococcus aureus, focusing on clinical respiratory isolates of methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains. Specifically, it sought to evaluate phage lytic activity, host range, stability, biofilm disruption capabilities, and overall safety for therapeutic use.

METHODS AND RESULTS

Novel phages, Koomba kaat 1 and Biyabeda mokiny 1, were identified and characterized using microbiological assays and bioinformatics. They exhibited lytic activity against clinical MSSA and MRSA isolates, disrupted biofilms from airway isolates, remained stable for at least one year in storage, and could be aerosolized without significant reductions in activity. Bioinformatic tools were used to assess safety, lifecycle, virulence, and prophage contamination when grown using their original isolation host. Receptor binding proteins within their genomes were also predicted, providing insight into their mechanisms of action. Both phages demonstrated strong efficacy against the clinical isolates tested and demonstrated robust stability under storage and delivery conditions.

CONCLUSIONS

Koomba kaat 1 and Biyabeda mokiny 1 are promising candidates for phage therapy. Their efficacy against clinical S. aureus isolates, ability to break down biofilm, and stability for airway implementation, positions them as valuable tools for addressing persistent airway infections caused by S. aureus.

摘要

目的

本研究旨在鉴定可用于治疗金黄色葡萄球菌的噬菌体,重点关注临床呼吸道分离出的甲氧西林敏感(MSSA)和甲氧西林耐药(MRSA)菌株。具体而言,该研究旨在评估噬菌体的裂解活性、宿主范围、稳定性、生物膜破坏能力以及治疗用途的整体安全性。

方法与结果

通过微生物学检测和生物信息学鉴定并表征了新型噬菌体Koomba kaat 1和Biyabeda mokiny 1。它们对临床MSSA和MRSA分离株表现出裂解活性,破坏了气道分离株的生物膜,在储存中至少稳定一年,并且雾化后活性无显著降低。使用生物信息学工具评估了使用其原始分离宿主培养时的安全性、生命周期、毒力和前噬菌体污染情况。还预测了其基因组中的受体结合蛋白,从而深入了解其作用机制。两种噬菌体对测试的临床分离株均显示出强大的疗效,并且在储存和递送条件下表现出强大的稳定性。

结论

Koomba kaat 1和Biyabeda mokiny 1是噬菌体疗法的有前景的候选者。它们对临床金黄色葡萄球菌分离株的疗效、分解生物膜的能力以及在气道应用中的稳定性,使其成为解决由金黄色葡萄球菌引起的持续性气道感染的有价值工具。

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