Toward a Phage Cocktail for Tuberculosis: Susceptibility and Tuberculocidal Action of Mycobacteriophages against Diverse Mycobacterium tuberculosis Strains.
Toward a Phage Cocktail for Tuberculosis: Susceptibility and Tuberculocidal Action of Mycobacteriophages against Diverse Mycobacterium tuberculosis Strains.
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DOI：
10.1128/mbio.00973-21
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发表时间：
2021-05-20
期刊：
影响因子：
6.4
通讯作者：
Hatfull GF
中科院分区：
文献类型：
--
作者：
Guerrero-Bustamante CA;Dedrick RM;Garlena RA;Russell DA;Hatfull GF
人类结核病（TB）的全球健康负担及其病原体结核分枝杆菌（Mycobacterium tuberculosis）的广泛抗生素耐药性需要新的结核病控制策略。成功使用噬菌体鸡尾酒治疗结核分枝杆菌感染表明，结核分枝杆菌可以在结核病治疗中发挥作用。为了组装具有结核病最佳治疗潜力的噬菌体鸡尾酒，我们探索了分枝杆菌噬菌体的多样性，以鉴定出具有杀结核活性的噬菌体，并确定了跨越结核分枝杆菌复合体的人类适应菌株的主要谱系的多种菌株的噬菌体感染谱。使用基因组工程和噬菌体遗传学的组合，我们已经组装了一个五噬菌体鸡尾酒，最大限度地减少噬菌体耐药性和交叉耐药性的出现，以多种抗生素，并有效地杀死M。结核菌株测试。此外，这些细菌在不拮抗抗生素效力的情况下起作用，并且感染异烟肼抗性菌株和敏感菌株。
The global health burden of human tuberculosis (TB) and the widespread antibiotic resistance of its causative agent Mycobacterium tuberculosis warrant new strategies for TB control. The successful use of a bacteriophage cocktail to treat a Mycobacterium abscessus infection suggests that phages could play a role in tuberculosis therapy. To assemble a phage cocktail with optimal therapeutic potential for tuberculosis, we have explored mycobacteriophage diversity to identify phages that demonstrate tuberculocidal activity and determined the phage infection profiles for a diverse set of strains spanning the major lineages of human-adapted strains of the Mycobacterium tuberculosis complex. Using a combination of genome engineering and bacteriophage genetics, we have assembled a five-phage cocktail that minimizes the emergence of phage resistance and cross-resistance to multiple phages, and which efficiently kills the M. tuberculosis strains tested. Furthermore, these phages function without antagonizing antibiotic effectiveness, and infect both isoniazid-resistant and -sensitive strains.