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Isolation and Characterization of Novel Escherichia coli O157:H7 Phage SPEC13 as a Therapeutic Agent for E. coli Infections In Vitro and In Vivo

机译:新型大肠杆菌 O157:H7 噬菌体 SPEC13 的分离和表征作为体外和体内大肠杆菌感染的治疗剂

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摘要

Escherichia coli O157:H7 is a recognized food-borne pathogen causing severe food poisoning at low doses. Bacteriophages (phages) are FDA-approved for use in food and are suggested as natural preservatives against specific pathogens. A novel phage must be identified and studied to develop a new natural preservative or antimicrobial agent against E. coli O157:H7. The phage SPEC13 displayed broad host range and was classified within the Ackermannviridae family based on its observed characteristics by a TEM and genome analysis. In 10 min, this phage achieves a remarkable 93% adsorption rate with the host. Its latency period then lasts about 20 min, after which it bursts, releasing an average of 139 ± 3 PFU/cell. It exhibited robustness within a pH range of 4 to 12, indicating resilience under diverse environmental circumstances. Furthermore, SPEC13 demonstrated stability at an ambient temperature up to 60 °C. A whole genome and phylogenetics analysis revealed that SPEC13 is a novel identified phage, lacking a lysogenic life cycle, antibiotic resistance genes, or genes associated with virulence, thereby presenting a promising biological agent for therapeutic application. Animal studies showed that SPEC13 effectively controlled the growth of harmful bacteria, resulting in a significant improvement in colon health, marked by reduced swelling (edema) and tissue damage (mucosal injury). The introduction of SPEC13 resulted in a substantial decrease in quantities of E. coli O157:H7, reducing the bacterial load to approximately 5 log CFU/g of feces. In conclusion, SPEC13 emerges as a promising inclusion in the array of phage therapy, offering a targeted and efficient approach for addressing bacterial infections.
机译:大肠杆菌 O157:H7 是一种公认的食源性病原体,低剂量时可引起严重食物中毒。噬菌体(噬菌体)已获得 FDA 批准用于食品,并被建议作为针对特定病原体的天然防腐剂。必须鉴定和研究新型噬菌体,以开发针对大肠杆菌 O157:H7 的新型天然防腐剂或抗菌剂。噬菌体 SPEC13 显示出广泛的宿主范围,并根据其通过 TEM 和基因组分析观察到的特征被归入 Ackermannviridae 家族。在 10 分钟内,该噬菌体与宿主的吸附率达到了惊人的 93%。然后它的延迟期持续约 20 分钟,之后它会突发,平均释放 139 ± 3 PFU/单元。它在 4 至 12 的 pH 范围内表现出稳健性,表明在各种环境条件下具有弹性。此外,SPEC13 在高达 60 °C 的环境温度下表现出稳定性。 全基因组和系统发育分析显示,SPEC13 是一种新型鉴定的噬菌体,缺乏溶原生命周期、抗生素耐药基因或与毒力相关的基因,因此是一种有前途的生物制剂用于治疗应用。动物研究表明,SPEC13 有效控制有害细菌的生长,从而显着改善结肠健康,其特点是减少肿胀(水肿)和组织损伤(粘膜损伤)。SPEC13 的引入导致 E 的数量大幅减少。大肠杆菌 O157:H7,将细菌载量降低到大约 5 log CFU/g 粪便。总之,SPEC13 成为噬菌体疗法系列中一个很有前途的内含物,为解决细菌感染提供了一种靶向和有效的方法。

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