Chen Feng, Cheng Xingjun, Li Jianbo, Yuan Xiefang, Huang Xiuhua, Lian Mao, Li Wenfang, Huang Tianfang, Xie Yaliu, Liu Jie, Gao Pan, Wei Xiawei, Wang Zhenling, Wu Min
Respiratory Department, Allergy and Immunity Institute, Affiliated Hospital, Southwest Medical University, 646000, Luzhou, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.
J Virol. 2021 Mar 25;95(8). doi: 10.1128/JVI.01832-20. Epub 2021 Jan 20.
With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of with multi-drug resistance (MDR) both and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) , and antibacterial capacity both and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria but also significantly reduce the infection symptom and disease progression , including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR
随着严重抗生素耐药性的迅速出现以及新型抗菌药物发现的滞后，用于治疗病原菌感染的噬菌体疗法在临床上受到了极大关注。然而，治疗性噬菌体的开发也面临严峻挑战，例如筛选过程繁琐以及生产有效噬菌体药物耗时长久，因为每种噬菌体可能仅能裂解范围狭窄的细菌菌株。鉴定具有广泛宿主范围的高效噬菌体对于改善噬菌体疗法至关重要。在此，我们从各种环境中分离并鉴定了几种裂解性噬菌体，通过测试它们的生长、侵袭、宿主范围以及杀灭靶向细菌的潜力，这些噬菌体对[具体细菌名称未给出]具有特异性。重要的是，我们鉴定出了几种具有广泛宿主范围的治疗性噬菌体（HX1、PPY9和TH15），它们能够在体外和小鼠模型中裂解[具体细菌名称未给出]的实验室菌株和多重耐药（MDR）临床分离株。此外，我们通过基因组测序以及针对已知噬菌体的后续计算分析，分析了与高水平广泛宿主覆盖相关的关键遗传特征。总体而言，我们的研究结果表明，这些新型噬菌体对于那些对传统治疗无反应的患者可能具有作为治疗选择进一步开发的潜力。从各种环境中分离出的新型裂解性噬菌体在关键遗传特征、形态结构、针对实验室菌株和临床多重耐药（MDR）[具体细菌名称未给出]的宿主范围以及体外和小鼠模型中的抗菌能力等方面进行了系统鉴定。首先，我们鉴定了遗传特征并与其他现有噬菌体进行比较。此外，我们利用实验室菌株PAO1诱导的急性肺炎以及MDR临床分离株W19，还有由负载FDR1（从囊性纤维化（CF）患者痰液中分离出的黏液样表型菌株）的琼脂珠诱导的慢性肺炎。结果，我们发现这些噬菌体不仅能在体外抑制细菌，还能显著减轻感染症状和疾病进展，包括降低小鼠体内的细菌负荷、炎症反应和肺损伤，这表明它们可能被进一步开发为针对MDR[具体细菌名称未给出]的治疗剂
