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首个噬菌体vB-ApyS-JF1显示出作为感染替代治疗策略的潜力。

vB-ApyS-JF1, the First Phage, Shows Potential as an Alternative Treatment Strategy for Infections.

作者信息

Ji Yalu, Song Liran, Zhou Zuoyong, Liu Xiao, Li Fengyang, Guo Zhimin, Guan Yuan, Yang Li, Feng Xin, Sun Changjiang, Lei Liancheng, Han Wenyu, Gu Jingmin

机构信息

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

College of Veterinary Medicine, Southwest University, Chongqing, China.

出版信息

Front Microbiol. 2021 Oct 25;12:736304. doi: 10.3389/fmicb.2021.736304. eCollection 2021.

Abstract

Trueperella () is an important opportunistic animal pathogen that causes huge economic losses to the animal husbandry industry. The emergence of bacterial resistance and the unsatisfactory effect of the vaccine have prompted investigators to explore alternative strategies for controlling infection. Due to the ability of phages to kill multidrug-resistant bacteria, the use of phage therapy to combat multidrug-resistant bacterial infections has attracted attention. In this study, a phage, vB-ApyS-JF1 (JF1), was isolated from sewage samples, and its whole genome and biological characteristics were elucidated. Moreover, the protective effect of phage JF1 on a mouse bacteremic model caused by was studied. JF1 harbors a double-stranded DNA genome with a length of 90,130 bp (30.57% G + C). The genome of JF1 lacked bacterial virulence-, antibiotic resistance- and lysogenesis-related genes. Moreover, the genome sequence of JF1 exhibited low coverage (<6%) with all published phages in the NCBI database, and a phylogenetic analysis of the terminase large subunits and capsid indicated that JF1 was evolutionarily distinct from known phages. In addition, JF1 was stable over a wide range of pH values (3 to 11) and temperatures (4 to 50°C) and exhibited strong lytic activity against . In murine experiments, a single intraperitoneal administration of JF1 30 min post-inoculation provided 100% protection for mice against infection. Compared to the phosphate-buffered saline (PBS) treatment group, JF1 significantly ( < 0.01) reduced the bacterial load in the blood and tissues of infected mice. Meanwhile, treatment with phage JF1 relieved the pathological symptoms observed in each tissue. Furthermore, the levels of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-6 (IL-6) in the blood of infected mice were significantly ( < 0.01) decreased in the phage-treated group. Taken together, these results indicate that phage JF1 demonstrated great potential as an alternative therapeutic treatment against infection.

摘要

特鲁珀菌属(Trueperella )是一种重要的机会性动物病原体,给畜牧业造成巨大经济损失。细菌耐药性的出现以及疫苗效果不尽人意促使研究人员探索控制感染的替代策略。由于噬菌体具有杀死多重耐药菌的能力,利用噬菌体疗法对抗多重耐药菌感染受到关注。在本研究中,从污水样本中分离出一株特鲁珀菌噬菌体vB - ApyS - JF1(JF1),并阐明了其全基因组和生物学特性。此外,研究了噬菌体JF1对由特鲁珀菌属引起的小鼠菌血症模型的保护作用。JF1含有一个长度为90,130 bp(G + C含量为30.57%)的双链DNA基因组。JF1的基因组缺乏细菌毒力、抗生素抗性和溶原性相关基因。此外,JF1的基因组序列与NCBI数据库中所有已发表的噬菌体的覆盖率较低(<6%),对末端酶大亚基和衣壳的系统发育分析表明JF1在进化上与已知噬菌体不同。此外,JF1在较宽的pH值范围(3至11)和温度范围(4至50°C)内稳定,并对特鲁珀菌属表现出强大的裂解活性。在小鼠实验中,接种后30分钟单次腹腔注射JF1为小鼠提供了100%的保护,使其免受特鲁珀菌属感染。与磷酸盐缓冲盐水(PBS)处理组相比,JF1显著(P < 0.01)降低了感染小鼠血液和组织中的细菌载量。同时,用噬菌体JF1治疗缓解了在每个组织中观察到的病理症状。此外,在噬菌体治疗组中,感染小鼠血液中炎性细胞因子肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和白细胞介素-6(IL-6)的水平显著(P < 0.01)降低。综上所述,这些结果表明噬菌体JF1作为对抗特鲁珀菌属感染的替代治疗方法具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c082/8573968/11965291ca05/fmicb-12-736304-g001.jpg

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