Alseth Ellinor O, Roush Carli, Irby Iris, Kopylov Mykhailo, Bobe Daija, Diggs Monneh W, Nguyen Kristy, Xu Huaijin, Schmidt-Krey Ingeborg, Bryksin Anton V, Rather Philip N
Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
PLoS Pathog. 2025 Apr 10;21(4):e1012986. doi: 10.1371/journal.ppat.1012986. eCollection 2025 Apr.
With the global rise of antimicrobial resistance, phage therapy is increasingly re-gaining traction as a strategy to treat bacterial infections. For phage therapy to be successful however, we first need to isolate appropriate candidate phages for both clinical and experimental research. Acinetobacter baumannii is an opportunistic pathogen known for its ability to rapidly evolve resistance to antibiotics, making it a prime target for phage therapy. Yet phage isolation may be hampered by A. baumannii's ability to rapidly switch between capsular states. Here, we report the discovery and structural characterisation of a novel lytic phage, Mystique. This phage was initially isolated against the wild-type AB5075: a commonly used clinical model strain. When screening Mystique on 103 highly diverse isolates of A. baumannii, we found that it has a broad host range, being able to infect 85.4% of all tested strains when tested on bacterial lawns - a host range that expanded to 91.3% when tested in liquid culture. This variation between solid and liquid culturing conditions on phage infectivity was also observed for several other phages in our collection that were assumed unable to infect AB5075, and some capsule negative mutants that seemed resistant to Mystique proved susceptible when assayed in liquid. This highlights how differences in culturing conditions can drastically impact phage infectivity, with important consequences for phage isolation and characterisation efforts. Finally, Mystique was found to be able to infect other species of Acinetobacter, making it a multi-species phage with broad applicability for further research.
随着全球抗菌药物耐药性的上升，噬菌体疗法作为一种治疗细菌感染的策略正越来越受到关注。然而，要使噬菌体疗法取得成功，我们首先需要分离出适合临床和实验研究的候选噬菌体。鲍曼不动杆菌是一种机会致病菌，以其能迅速产生抗生素耐药性而闻名，这使其成为噬菌体疗法的主要目标。然而，鲍曼不动杆菌能够在荚膜状态之间快速转换，这可能会阻碍噬菌体的分离。在此，我们报告了一种新型裂解性噬菌体——“神秘号”的发现及其结构特征。这种噬菌体最初是针对野生型AB5075分离得到的，AB5075是一种常用的临床模型菌株。当在103株高度多样化的鲍曼不动杆菌菌株上筛选“神秘号”时，我们发现它具有广泛的宿主范围，在细菌平板上测试时，能够感染所有测试菌株的85.4%，在液体培养中测试时，宿主范围扩大到91.3%。我们收集的其他几种噬菌体在固体和液体培养条件下对噬菌体感染性也存在这种差异，这些噬菌体原本被认为无法感染AB5075，一些看似对“神秘号”有抗性的荚膜阴性突变体在液体培养中检测时却被证明是敏感的。这凸显了培养条件的差异会如何极大地影响噬菌体的感染性，对噬菌体的分离和鉴定工作产生重要影响。最后，发现“神秘号”能够感染其他不动杆菌属物种，使其成为一种具有广泛适用性的多物种噬菌体，可用于进一步研究。
