Laboratory of Phage Therapy, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Kładki 24, 80-822 Gdansk, Poland; Department of Medical Mirobiology, Faculty of Medicine, Medical University of Gdańsk, Dębowa 25, 80-204 Gdansk, Poland.
Department of Molecular Biology, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland; Department of Cell Biology and Immunology, Intercollegiate Faculty of Biotechnology of University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211 Gdańsk, Poland.
Microbiol Res. 2022 Aug;261:127052. doi: 10.1016/j.micres.2022.127052. Epub 2022 May 4.
In light of spreading antibiotic resistance among pathogenic bacteria, the development of novel approaches to combat such microorganisms is crucial. Salmonella enterica is pathogenic to humans, however, it can also infect poultry, being a potential foodborne pathogen when poultry-derived food is contaminated by this bacterium. Phage therapy is one of the alternative ways to treat Salmonella-infected animals while the establishment of this method and its introduction to a general practice requires detailed studies on safety and efficacy. Here, we present the results of such studies with two previously isolated and characterized bacteriophages, vB_SenM2 and vB_Sen-TO17, and four strains of S. enterica belonging to two serovars, Typhimurium and Enteritidis. We demonstrated effective reduction of bacterial cell number and cell culture density when using each phage alone, and in combination (as a cocktail). These phages were also effective in reducing bacterial biofilm. The efficacy of this in vitro phage therapy was compared to the action of known antibiotics, as was the efficiency of appearance of bacteria resistant to both these types of antibacterial agents. Safety of the use of bacteriophages was demonstrated using the LAL chromogenic test and the chicken fibroblast viability assay. Finally, the efficacy of phage therapy was assessed with the in vivo model of S. enterica-infected Galleria mellonella larvae, showing a significant improvement in the survival of the animals. In conclusion, we demonstrated high efficacy and acceptable safety profiles of phage therapy against S. enterica strains using vB_SenM-2 and vB_Sen-TO17 phages (both alone and in a cocktail). These results open a possibility for a trial with the use of poultry and these phages which might potentially allow to introduce of this method for practical use in poultry farming.
鉴于病原菌对抗生素的耐药性不断扩散，开发新型方法来对抗这些微生物至关重要。沙门氏菌对人类具有致病性，但它也可以感染家禽，当家禽源性食品被这种细菌污染时，它就成为一种潜在的食源性致病菌。噬菌体疗法是治疗感染沙门氏菌的动物的一种替代方法，而这种方法的建立和引入一般实践需要对安全性和疗效进行详细研究。在这里，我们展示了之前分离和表征的两种噬菌体 vB_SenM2 和 vB_Sen-TO17 以及属于两个血清型鼠伤寒和肠炎的四种沙门氏菌菌株的研究结果。我们证明了单独使用每种噬菌体以及组合使用（作为鸡尾酒）时，都能有效减少细菌数量和细胞培养密度。这些噬菌体还能有效减少细菌生物膜。将这种体外噬菌体疗法的疗效与已知抗生素的作用进行了比较，并比较了两种类型的抗菌剂都产生耐药性的细菌的出现效率。使用 LAL 显色试验和鸡成纤维细胞活力测定法证明了噬菌体使用的安全性。最后，使用感染 S. enterica 的 Galleria mellonella 幼虫的体内模型评估了噬菌体治疗的疗效，结果显示动物的存活率显著提高。总之，我们使用 vB_SenM-2 和 vB_Sen-TO17 噬菌体（单独使用和鸡尾酒使用）证明了针对 S. enterica 菌株的噬菌体疗法具有高效性和可接受的安全性。这些结果为使用家禽和这些噬菌体进行试验提供了可能性，这可能使该方法能够引入家禽养殖的实际应用。
