Wang Xinwu, Ji Yalu, Su Jizuo, Xue Yibing, Xi Hengyu, Wang Zijing, Bi Lanting, Zhao Rihong, Zhang Hao, Yang Li, Guo Zhimin, Guan Yuan, Feng Xin, Sun Changjiang, Lei Liancheng, Ur Rahman Sadeeq, Dong Jianbao, Han Wenyu, Gu Jingmin
Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China.
Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, People's Republic of China.
Appl Environ Microbiol. 2020 Oct 28;86(22). doi: 10.1128/AEM.01366-20.
subsp. serovar Abortusequi is a frequently reported pathogen causing abortion in mares. In this study, the preventive and therapeutic effects of phage P SAE-01E2 against Abortusequi in a mouse model of abortion were investigated. Phage P SAE-01E2 was stable at different temperatures (4 to 70°C) and pH values (pH 4 to 10) and could lyse the majority of the serogroup O:4 and O:9 strains tested (25/28). There was no lysogeny-related, toxin, or antibiotic resistance-related gene in the genome of P SAE-01E2. All of these characteristics indicate that P SAE-01E2 has the potential for use in phage therapy. In experiments, 2 × 10 CFU/mouse of Abortusequi ATCC 9842 was sufficient to lead to murine abortion (gestational day 14.5) within 48 h. A single intraperitoneal inoculation of P SAE-01E2 (10 PFU/mouse, multiplicity of infection = 10) 1 h before or after Abortusequi challenge provided effective protection to all pregnant mice (10/10). After 24 h of treatment with phage P SAE-01E2, the bacterial loads in both the placenta and the uterus of the infected mice were significantly decreased (<10 CFU/g) compared to those in the placenta and the uterus of the mice in the control group (>10 CFU/g). In addition, the levels of inflammatory cytokines in the placenta and blood of the mice in the phage administration groups were significantly reduced (0.05) compared to those in the placenta and blood of the mice in the control group. Altogether, these findings indicate that P SAE-01E2 shows the potential to block abortions induced by Abortusequi Abortusequi is an important pathogen that can induce abortions in mares. Although Abortusequi has been well controlled in Europe and the United States due to strict breeding and health policies, it is still widespread in African and Asian countries and has proven difficult to control. In China, abortions caused by Abortusequi have also been reported in donkeys. So far, there is no commercial vaccine. Thus, exploiting alternative efficient and safe strategies to control Abortusequi infection is essential. In this study, a new lytic phage, P SAE-01E2, infecting Abortusequi was isolated, and the characteristics of P SAE-01E2 indicated that it has the potential for use in phage therapy. A single intraperitoneal inoculation of P SAE-01E2 before or after Abortusequi challenge provided effective protection to all pregnant mice. Thus, P SAE-01E2 showed the potential to block abortions induced by Abortusequi .
亚种血清型马流产嗜性杆菌是一种经常报道的可导致母马流产的病原体。在本研究中，研究了噬菌体P SAE - 01E2在流产小鼠模型中对马流产嗜性杆菌的预防和治疗效果。噬菌体P SAE - 01E2在不同温度（4至70°C）和pH值（pH 4至10）下稳定，并且能够裂解所测试的大多数O:4和O:9血清群菌株（25/28）。P SAE - 01E2的基因组中没有与溶原性、毒素或抗生素抗性相关的基因。所有这些特征表明P SAE - 01E2具有用于噬菌体治疗的潜力。在实验中，每只小鼠接种2×10⁶CFU的马流产嗜性杆菌ATCC 9842足以在48小时内导致小鼠流产（妊娠第14.5天）。在马流产嗜性杆菌攻击前或攻击后1小时单次腹腔注射P SAE - 01E2（10⁹PFU/小鼠，感染复数= 10）为所有怀孕小鼠（10/10）提供了有效的保护。在用噬菌体P SAE - 01E2治疗24小时后，与对照组小鼠胎盘和子宫中的细菌载量（>10⁶CFU/g）相比，感染小鼠胎盘和子宫中的细菌载量显著降低（<10³CFU/g）。此外，与对照组小鼠胎盘和血液中的炎症细胞因子水平相比，噬菌体给药组小鼠胎盘和血液中的炎症细胞因子水平显著降低（P < 0.05）。总之，这些发现表明P SAE - 01E2具有阻断马流产嗜性杆菌诱导流产的潜力。马流产嗜性杆菌是一种可导致母马流产的重要病原体。尽管由于严格的育种和健康政策，马流产嗜性杆菌在欧洲和美国已得到很好的控制，但它在非洲和亚洲国家仍然广泛存在，并且已证明难以控制。在中国，也有关于驴因马流产嗜性杆菌导致流产的报道。到目前为止，还没有商业疫苗。因此，开发替代的高效和安全策略来控制马流产嗜性杆菌感染至关重要。在本研究中，分离出一种新的裂解性噬菌体P SAE - 01E2，其感染马流产嗜性杆菌，P SAE - 01E2的特性表明它具有用于噬菌体治疗的潜力。在马流产嗜性杆菌攻击前或攻击后单次腹腔注射P SAE - 01E2为所有怀孕小鼠提供了有效的保护。因此，P SAE - 01E2显示出阻断马流产嗜性杆菌诱导流产的潜力。
