Martinez-Soto Carlos E, McClelland Michael, Kropinski Andrew M, Lin Janet T, Khursigara Cezar M, Anany Hany
Guelph Research and Development Centre, Agriculture and Agri-Food Canada, 93 Stone Rd W, N1G 5C9, Guelph, Ontario, Canada.
Department of Molecular and Cellular Biology, College of Biological Science, University of Guelph, 50 Stone Rd E, N1G 2W1, Guelph, Ontario, Canada.
Microlife. 2024 Mar 21;5:uqae003. doi: 10.1093/femsml/uqae003. eCollection 2024.
Non-Typhoidal (NTS) is one of the most common food-borne pathogens worldwide, with poultry products being the major vehicle for pathogenesis in humans. The use of bacteriophage (phage) cocktails has recently emerged as a novel approach to enhancing food safety. Here, a multireceptor phage cocktail of five phages was developed and characterized. The cocktail targets four receptors: O-antigen, BtuB, OmpC, and rough strains. Structural analysis indicated that all five phages belong to unique families or subfamilies. Genome analysis of four of the phages showed they were devoid of known virulence or antimicrobial resistance factors, indicating enhanced safety. The phage cocktail broad antimicrobial spectrum against , significantly inhibiting the growth of all 66 strains from 20 serovars tested . The average bacteriophage insensitive mutant (BIM) frequency against the cocktail was 6.22 × 10 in . Enteritidis, significantly lower than that of each of the individual phages. The phage cocktail reduced the load of in inoculated chicken skin by 3.5 log CFU/cm after 48 h at 25°C and 15°C, and 2.5 log CFU/cm at 4°C. A genome-wide transduction assay was used to investigate the transduction efficiency of the selected phage in the cocktail. Only one of the four phages tested could transduce the kanamycin resistance cassette at a low frequency comparable to that of phage P22. Overall, the results support the potential of cocktails of phage that each target different host receptors to achieve complementary infection and reduce the emergence of phage resistance during biocontrol applications.
非伤寒沙门氏菌（NTS）是全球最常见的食源性病原体之一，禽肉产品是其在人类中致病的主要载体。噬菌体鸡尾酒疗法最近已成为一种提高食品安全的新方法。在此，开发并表征了一种由五种噬菌体组成的多受体噬菌体鸡尾酒。该鸡尾酒靶向四种受体：O抗原、BtuB、OmpC和粗糙菌株。结构分析表明，所有五种噬菌体都属于独特的科或亚科。对其中四种噬菌体的基因组分析表明，它们没有已知的毒力或抗菌抗性因子，表明安全性更高。该噬菌体鸡尾酒具有广泛的抗菌谱，能显著抑制所测试的来自20个血清型的所有66株菌株的生长。针对该鸡尾酒的平均噬菌体不敏感突变体（BIM）频率为6.22×10⁻⁹。肠炎沙门氏菌的BIM频率显著低于每种单个噬菌体。在25°C和15°C下48小时后，该噬菌体鸡尾酒使接种鸡皮中的肠炎沙门氏菌载量降低了3.5 log CFU/cm²，在4°C下降低了2.5 log CFU/cm²。使用全基因组转导试验来研究该鸡尾酒中所选噬菌体的转导效率。所测试的四种噬菌体中只有一种能够以与噬菌体P22相当的低频转导卡那霉素抗性盒。总体而言，结果支持了针对不同宿主受体的噬菌体鸡尾酒在生物防治应用中实现互补感染并降低噬菌体抗性出现的潜力。
