Doub James B, Dunbar Dakarai, Jain Sara, Manchester Maggie, Berle Lila, Madhiwala Janvi, Anderson Bradley, Malick Riva, Jacobs Max, Urish Kenneth L
The Doub Laboratory of Translational Bacterial Research, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Clin Med. 2025 Aug 8;14(16):5609. doi: 10.3390/jcm14165609.
necrotizing fasciitis is a life-threatening infection requiring aggressive surgical and medical management. Despite these interventions, tremendous morbidity and mortality occur. Thus, novel agents are needed to reduce these negative outcomes. Consequently, the aims of this translational study were to evaluate the feasibility of using bacteriophages and the potential clinical ramifications of using bacteriophages in treatment of necrotizing fasciitis. Necrotizing fasciitis clinical isolates (n = 6) were tested against different Staphylococcal bacteriophages (n = 4) to assess for activity. After exposure to bacteriophages that had growth inhibition for more than 16 h, the ability of to change phenotypic expression of numerous enzymes was evaluated, and the ability to reduce bacterial virulence was measured with the assay. Staphylococcal myoviridae bacteriophages were able to lyse most clinical isolates (83%). Interestingly, after exposure to myoviridae bacteriophages, isolates had no expression of hemolysin, secreted coagulase, or lecthinase, or the ability to ferment mannitol. These same bacteriophages also caused statistically significant decreases in bacterial virulence ( < 0.05). Neither findings were observed for bacteriophages of the podoviridae family. To use bacteriophages for necrotizing fasciitis, cocktails of Staphylococcal myoviridae are likely needed to allow for broad host ranges, mitigating the need for in vitro sensitivity testing. Moreover, Staphylococcal myoviridae have the potential to reduce specific enzyme expression and global virulence of residual . Thus, bacteriophages may aid in reducing necrotizing fasciitis morbidity by not only lysing but also by reducing virulence.
坏死性筋膜炎是一种危及生命的感染，需要积极的手术和药物治疗。尽管采取了这些干预措施，但仍会出现极高的发病率和死亡率。因此，需要新型药物来减少这些不良后果。因此，这项转化研究的目的是评估使用噬菌体的可行性以及使用噬菌体治疗坏死性筋膜炎的潜在临床影响。对坏死性筋膜炎临床分离株（n = 6）进行针对不同葡萄球菌噬菌体（n = 4）的测试以评估活性。在暴露于具有超过16小时生长抑制作用的噬菌体后，评估其改变多种酶表型表达的能力，并用该试验测量其降低细菌毒力的能力。葡萄球菌肌尾噬菌体能够裂解大多数临床分离株（83%）。有趣的是，在暴露于肌尾噬菌体后，分离株没有溶血素、分泌型凝固酶或卵磷脂酶的表达，也没有发酵甘露醇的能力。这些相同的噬菌体还导致细菌毒力出现统计学上的显著下降（P < 0.05）。对于短尾噬菌体科的噬菌体，未观察到这些结果。为了将噬菌体用于坏死性筋膜炎的治疗，可能需要葡萄球菌肌尾噬菌体鸡尾酒来实现广泛的宿主范围，从而减少体外敏感性测试的需求。此外，葡萄球菌肌尾噬菌体有可能降低残余细菌的特定酶表达和总体毒力。因此，噬菌体不仅可以通过裂解细菌，还可以通过降低细菌毒力来帮助降低坏死性筋膜炎的发病率。
