College of Resources and Environment, Fujian Agriculture and Forestry University, Fuzhou, China.
Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University, Fuzhou, China.
mSystems. 2024 Sep 17;9(9):e0060724. doi: 10.1128/msystems.00607-24. Epub 2024 Aug 21.
The global rise of antibiotic resistance has renewed interest in phage therapy, as an alternative to antibiotics to eliminate multidrug-resistant (MDR) bacterial pathogens. However, optimizing the broad-spectrum efficacy of phage therapy remains a challenge. In this study, we addressed this issue by employing strategies to improve antimicrobial efficacy of phage therapy against MDR strains, which are notorious for their resistance to conventional antibiotics. This includes the selection of broad host range phages, optimization of phage formulation, and combinations with last-resort antibiotics. Our findings unveil that having a broad host range was a dominant trait of isolated phages, and increasing phage numbers in combination with antibiotics significantly enhanced the suppression of bacterial growth. The decreased incidence of bacterial infection was explained by a reduction in pathogen density and emergence of bacterial resistance. Furthermore, phage-antibiotic synergy (PAS) demonstrated considerable broad-spectrum antibacterial potential against different clades of clinical MDR pathogens. The improved treatment outcomes of optimized PAS were also evident in a murine model, where mice receiving optimized PAS therapy demonstrated a reduced bacterial burden in mouse tissues. Taken together, these findings offer an important development in optimizing PAS therapy and its efficacy in the elimination of MDR pathogens.
The worldwide spread of antimicrobial resistance (AMR) has posed a great challenge to global public health. Phage therapy has become a promising alternative against difficult-to-treat pathogens. One important goal of this study was to optimize the therapeutic efficiency of phage-antibiotic combinations, known as phage-antibiotic synergy (PAS). Through comprehensive analysis of the phenotypic and genotypic characteristics of a large number of CRKp-specific phages, we developed a systematic model for phage cocktail combinations. Crucially, our finding demonstrated that PAS treatments not only enhance the bactericidal effects of colistin and tigecycline against multidrug-resistant (MDR) strains in and context but also provide a robust response when antibiotics fail. Overall, the optimized PAS therapy demonstrates considerable potential in combating diverse pathogens, highlighting its relevance as a strategy to mitigate antibiotic resistance threats effectively.
抗生素耐药性在全球范围内的上升重新激发了人们对噬菌体疗法的兴趣，将其作为消除多药耐药（MDR）细菌病原体的抗生素替代品。然而，优化噬菌体疗法的广谱疗效仍然是一个挑战。在这项研究中，我们通过采用策略来提高噬菌体治疗针对 MDR 菌株的广谱疗效来解决这个问题，这些策略针对的是对传统抗生素具有耐药性的臭名昭著的 MDR 菌株。这包括选择广谱宿主范围噬菌体、优化噬菌体配方以及与最后手段抗生素联合使用。我们的研究结果表明，具有广谱宿主范围是分离噬菌体的主要特征，并且增加噬菌体数量与抗生素联合使用可显著增强抑制细菌生长的效果。病原体密度降低和细菌耐药性的出现解释了细菌感染发生率的降低。此外，噬菌体-抗生素协同作用（PAS）对不同临床 MDR 病原体的不同分支表现出相当大的广谱抗菌潜力。在小鼠模型中也观察到优化后的 PAS 治疗的改善治疗效果，接受优化后的 PAS 治疗的小鼠在其组织中的细菌负荷降低。综上所述，这些发现为优化 PAS 治疗及其在消除 MDR 病原体方面的疗效提供了重要的发展。
抗菌药物耐药性（AMR）的全球传播对全球公共健康构成了重大挑战。噬菌体疗法已成为治疗难治性病原体的一种有前途的替代方法。这项研究的一个重要目标是优化噬菌体-抗生素组合的治疗效率，即噬菌体-抗生素协同作用（PAS）。通过对大量 CRKp 特异性噬菌体的表型和基因型特征进行全面分析，我们开发了一种噬菌体鸡尾酒组合的系统模型。至关重要的是，我们的研究结果表明，PAS 治疗不仅增强了多粘菌素和替加环素对 MDR 菌株的杀菌效果，而且在抗生素失效时也提供了强大的反应。总的来说，优化后的 PAS 治疗在对抗多种 MDR 病原体方面具有相当大的潜力，凸显了其作为有效减轻抗生素耐药性威胁的策略的相关性。
