Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, 250100, China; Key Laboratory of Livestock and Poultry Multi-omics of MARA, China-UK Joint Laboratory of Bacteriophage Engineering, Jinan, 250100, China.
College of Animal Science and Technology, Shandong Agricultural University, Taian, 272018, China.
Poult Sci. 2024 Jul;103(7):103845. doi: 10.1016/j.psj.2024.103845. Epub 2024 May 13.
Phage therapy is gaining momentum as an alternative to antibiotics in the treatment of salmonellosis caused by Salmonella. In this study, a novel Salmonella phage, vB_SalS_JNS02, was isolated successfully from poultry farms in Shandong, China. The biological characteristics of vB_SalS_JNS02 were analysed, which revealed a short latent period of approximately 10 min and a burst size of 110 PFU/cell. Moreover, vB_SalS_JNS02 exhibited remarkable stability across a wide pH range (pH 3-12) and temperatures ranging from 30 to 80°C. Genome sequencing analysis provided valuable insights into the genetic composition of vB_SalS_JNS02, which consists of a double-stranded DNA genome that spans 42,450 base pairs and has a G + C content of 49.4%. Of significant importance, the genomic sequence of vB_SalS_JNS02 did not contain any genes related to lysogenicity, virulence, or antibiotic resistance. The phage's efficacy was evaluated in a larval challenge study. Treatment with the phage resulted in increased survival of Galleria mellonella larvae (100, 70, and 85%) (MOI 0.1) in the prophylactic treatment, co-infection treatment, and remedial treatment experiments, respectively. Another in vivo experiment investigated the potential application of the phage in broiler chickens and revealed that a single oral dose of vB_SalS_JNS02 (10 PFU/mL, 100 µL/chick) administered 3 h after S. enteritidis oral administration provided effective protection. The introduction of bacteriophage not only enhances the production of secretory immunoglobulin A (sIgA), but also induces alterations in the composition of the gut microbial community. Phage therapy increases the relative abundance of beneficial bacteria, which helps to maintain intestinal barrier homeostasis. However, it is unable to fully restore the disrupted intestinal microbiome caused by S. enteritidis infection. Importantly, no significant adverse effects were observed in the animal subjects following oral administration of the phage, and our findings highlight vB_SalS_JNS02 is a hopeful candidate as a promising tool to target Salmonella infections in poultry.
噬菌体疗法作为抗生素的替代品，在治疗由沙门氏菌引起的沙门氏菌病方面正逐渐受到重视。在这项研究中，从中国山东的家禽养殖场成功分离到了一种新型的沙门氏噬菌体 vB_SalS_JNS02。分析了 vB_SalS_JNS02 的生物学特性，结果表明其潜伏期约为 10 分钟，爆发量为 110 个 PFU/细胞。此外，vB_SalS_JNS02 在 pH 值为 3-12 和 30-80°C 的温度范围内表现出显著的稳定性。基因组测序分析提供了 vB_SalS_JNS02 的遗传组成的有价值的见解，该噬菌体由一个双链 DNA 基因组组成，跨度为 42450 个碱基对，GC 含量为 49.4%。值得注意的是，vB_SalS_JNS02 的基因组序列不包含任何与溶原性、毒性或抗生素耐药性相关的基因。在幼虫挑战研究中评估了噬菌体的疗效。在预防性治疗、共感染治疗和补救治疗实验中，用噬菌体处理后，大蜡螟幼虫的存活率分别提高了 100%、70%和 85%（MOI 0.1）。另一个体内实验研究了噬菌体在肉鸡中的潜在应用，结果表明，在肠炎沙门氏菌口服给药后 3 小时口服给予单剂量 vB_SalS_JNS02（10 PFU/mL，100 µL/只鸡）可提供有效保护。噬菌体的引入不仅增强了分泌型免疫球蛋白 A（sIgA）的产生，而且还诱导了肠道微生物群落组成的改变。噬菌体治疗增加了有益细菌的相对丰度，有助于维持肠道屏障的稳态。然而，它无法完全恢复肠炎沙门氏菌感染引起的肠道微生物组的破坏。重要的是，噬菌体口服给药后在动物体内未观察到明显的不良反应，我们的研究结果表明 vB_SalS_JNS02 是一种有前途的工具，可用于靶向家禽中的沙门氏菌感染。
