关键词: Clostridium perfringens Galleria mellonella bacteriophage therapy bacteriophages phage cocktails

Mesh : Clostridium perfringens / virology Animals Bacteriophages / physiology Clostridium Infections / microbiology therapy veterinary Host Specificity Poultry Diseases / microbiology virology Virulence Chickens Poultry / microbiology Phage Therapy / methods Larva / microbiology virology Disease Models, Animal

来  源:   DOI:10.1128/spectrum.03784-23   PDF(Pubmed)

Abstract:
Clostridium perfringens is a prevalent bacterial pathogen in poultry, and due to the spread of antimicrobial resistance, alternative treatments are needed to prevent and treat infection. Bacteriophages (phages), viruses that kill bacteria, offer a viable option and can be used therapeutically to treat C. perfringens infections. The aim of this study was to isolate phages against C. perfringens strains currently circulating on farms across the world and establish their virulence and development potential using host range screening, virulence assays, and larva infection studies. We isolated 32 phages of which 19 lysed 80%-92% of our global C. perfringens poultry strain collection (n = 97). The virulence of these individual phages and 32 different phage combinations was quantified in liquid culture at multiple doses. We then developed a multi-strain C. perfringens larva infection model, to mimic an effective poultry model used by the industry. We tested the efficacy of 16/32 phage cocktails in the larva model. From this, we identified that our phage cocktail consisting of phages CPLM2, CPLM15, and CPLS41 was the most effective at reducing C. perfringens colonization in infected larvae when administered before bacterial challenge. These data suggest that phages do have significant potential to prevent and treat C. perfringens infection in poultry.
OBJECTIVE: Clostridium perfringens causes foodborne illness worldwide, and 95% of human infections are linked to the consumption of contaminated meat, including chicken products. In poultry, C. perfringens infection causes necrotic enteritis, and associated mortality rates can be up to 50%. However, treating infections is difficult as the bacterium is becoming antibiotic-resistant. Furthermore, the poultry industry is striving toward reduced antibiotic usage. Bacteriophages (phages) offer a promising alternative, and to progress this approach, robust suitable phages and laboratory models that mimic C. perfringens infections in poultry are required. In our study, we isolated phages targeting C. perfringens and found that many lyse C. perfringens strains isolated from chickens worldwide. Consistent with other published studies, in the model systems we assayed here, when some phages were combined as cocktails, the infection was cleared most effectively compared to individual phage use.
摘要:
产气荚膜梭菌是禽类中普遍存在的细菌病原体,由于抗菌素耐药性的传播,需要替代疗法来预防和治疗感染。噬菌体(噬菌体),杀死细菌的病毒,提供了一个可行的选择,可以用于治疗产气荚膜梭菌感染。这项研究的目的是分离针对目前在世界各地农场中流通的产气荚膜梭菌菌株的噬菌体,并使用宿主范围筛选确定其毒力和发育潜力。毒力测定,和幼虫感染研究。我们分离了32个噬菌体,其中19个裂解了我们全球产气荚膜梭菌家禽菌株收集的80%-92%(n=97)。在多个剂量的液体培养物中定量这些个体噬菌体和32种不同噬菌体组合的毒力。然后我们开发了多菌株产气荚膜梭菌幼虫感染模型,模仿行业使用的有效家禽模型。我们在幼虫模型中测试了16/32噬菌体混合物的功效。由此,我们发现,由噬菌体CPLM2,CPLM15和CPLS41组成的噬菌体混合物在细菌攻击前给药时最有效地减少了产气荚膜梭菌在感染幼虫中的定植.这些数据表明噬菌体确实具有预防和治疗家禽产气荚膜梭菌感染的显著潜力。
目标:产气荚膜梭菌在全球范围内引起食源性疾病,95%的人类感染与食用受污染的肉类有关,包括鸡肉产品。在家禽中,产气荚膜梭菌感染引起坏死性肠炎,相关死亡率可高达50%。然而,治疗感染是困难的,因为细菌变得具有抗生素抗性。此外,家禽业正在努力减少抗生素的使用。噬菌体(噬菌体)提供了一个有希望的替代品,为了推进这种方法,需要模拟家禽产气荚膜梭菌感染的健壮合适的噬菌体和实验室模型。在我们的研究中,我们分离了针对产气荚膜梭菌的噬菌体,并发现了许多从世界各地的鸡中分离出的产气荚膜梭菌菌株。与其他已发表的研究一致,在我们这里分析的模型系统中,当一些噬菌体被组合成鸡尾酒时,与单个噬菌体使用相比,感染被最有效地清除。
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