Task Applied Science, Cape Town, South Africa.
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Respiration. 2022;101(1):1-15. doi: 10.1159/000519870. Epub 2021 Nov 23.
Rates of antimicrobial resistance are increasing globally while the pipeline of new antibiotics is drying up, putting patients with disease caused by drug-resistant bacteria at increased risk of complications and death. The growing costs for diagnosis and management of drug resistance threaten tuberculosis control where the disease is endemic and resources limited. Bacteriophages are viruses that attack bacteria. Phage preparations served as anti-infective agents long before antibiotics were discovered. Though small in size, phages are the most abundant and diverse biological entity on earth. Phages have co-evolved with their hosts and possess all the tools needed to infect and kill bacteria, independent of drug resistance. Modern biotechnology has improved our understanding of the biology of phages and their possible uses. Phage preparations are available to treat meat, fruit, vegetables, and dairy products against parasites or to prevent contamination with human pathogens, such as Listeria monocytogenes, Escherichia coli, or Staphylococcus aureus. Such phage-treated products are considered fit for human consumption. A number of recent case reports describe in great detail the successful treatment of highly drug-resistant infections with individualized phage preparations. Formal clinical trials with standardized products are slowly emerging. With its highly conserved genome and relative paucity of natural phage defence mechanisms Mycobacterium tuberculosis appears to be a suitable target for phage treatment. A phage cocktail with diverse and strictly lytic phages that kill all lineages of M. tuberculosis, and can be propagated on Mycobacterium smegmatis, has been assembled and is available for the evaluation of optimal dosage and suitable routes of administration for tuberculosis in humans. Phage treatment can be expected to be safe and active on extracellular organisms, but phage penetration to intracellular and granulomatous environments as well as synergistic effects with antibiotics are important questions to address during further evaluation.
抗生素耐药率在全球范围内不断上升，而新抗生素的研发却日渐枯竭，这使得耐药菌感染的患者面临更高的并发症和死亡风险。耐药性的诊断和管理成本不断增加，对结核病控制构成了威胁，而结核病在资源有限的地区流行。噬菌体是一种攻击细菌的病毒。在抗生素被发现之前，噬菌体制剂就已经被用作抗感染药物。虽然噬菌体体积小，但它们是地球上数量最多、种类最多样的生物实体。噬菌体与它们的宿主共同进化，并拥有感染和杀死细菌所需的所有工具，而不受耐药性的影响。现代生物技术提高了我们对噬菌体生物学及其潜在用途的认识。噬菌体制剂可用于治疗肉类、水果、蔬菜和乳制品中的寄生虫，或防止李斯特菌、大肠杆菌或金黄色葡萄球菌等人类病原体污染。经过噬菌体处理的产品被认为适合人类食用。最近有一些病例报告详细描述了使用个体化噬菌体制剂成功治疗高度耐药感染的情况。具有标准化产品的正式临床试验正在缓慢出现。由于结核分枝杆菌具有高度保守的基因组和相对较少的天然噬菌体防御机制，因此它似乎是噬菌体治疗的合适目标。已经组装了一种含有多种严格裂解噬菌体的噬菌体鸡尾酒，可在耻垢分枝杆菌上繁殖，可用于评估结核分枝杆菌在人类中的最佳剂量和合适的给药途径。噬菌体治疗预计在细胞外生物中是安全且有效的，但噬菌体穿透细胞内和肉芽肿环境以及与抗生素的协同作用是在进一步评估中需要解决的重要问题。
