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一种新型噬菌体鸡尾酒疗法治疗小鼠尿路感染模型。

A Novel Phage Cocktail Therapy of the Urinary Tract Infection in a Mouse Model.

机构信息

Department of Biology, College of Sciences, Mustansiriyah University, Baghdad, Iraq.

出版信息

Arch Razi Inst. 2021 Nov 30;76(5):1229-1236. doi: 10.22092/ari.2021.356004.1762. eCollection 2021 Nov.

Abstract

() is a major bacterial pathogen associated with many cases of serious infections, such as urinary tract infections (UTI) and meningitis intestinal. The rapid emergence of antimicrobial multidrug-resistant bacteria occurring worldwide has been attributed to the overuse of antibiotics. Alternative strategies must be developed to overcome antibiotic resistance. A promising alternative for the treatment of infections is the use of phages as antibacterial agents. A total of 90 female albino mice were randomly divided into three groups (n=30) and used for the induction of UTI. The animals were acclimatized in their cages for 24 h before inoculation and allowed to access chow and water freely. For UTI induction, the peri-urethral area was sterilized with 70% ethanol, and bacterial inoculation was then injected into the bladder through the urethra using a 24-gauge sterile Teflon catheter with an outer diameter of 0.7 mm and length of 19 mm. A single phage and a phage cocktail preparation have been evaluated for their therapeutic activity in the mouse model of chronic UTI induced by transurethral injection of two isolates of the uropathogenic 8 and 302. The results of the transurethral and intra-peritoneal injection of phage(s) that prepared on day 10 after the establishment of the mouse chronic model showed no effect of a single phage PEC80 in the treatment of UTI, whereas both administration routes of the phage cocktail preparation resulted in the clearance of bacteria from mice urine and homogenates of the urinary bladders and kidneys of the sacrificed mice after 24 h following the administration of phage cocktail dose. The high activity of the phage cocktail in the treatment of mouse chronic model of UTI is attributed to the broader host range of the phage cocktail, compared to the very narrow host range of the phage PEC80. It is concluded that the phage therapy by using phage preparations as the 25 phages cocktail evaluated in this study is a highly promising and potential alternative therapy for human UTIs.

摘要

()是一种与许多严重感染相关的主要细菌病原体,如尿路感染(UTI)和脑膜炎。抗生素的过度使用导致了世界范围内出现的抗微生物多药耐药细菌的迅速出现。必须开发替代策略来克服抗生素耐药性。噬菌体作为抗菌剂用于治疗感染是一种很有前途的替代方法。总共 90 只雌性白化病小鼠被随机分为三组(n=30),用于诱导 UTI。在接种前,动物在笼子中适应 24 小时,并允许自由进食和饮水。为了诱导 UTI,用 70%乙醇对尿道周围区域进行消毒,然后通过尿道用外径为 0.7 毫米、长 19 毫米的 24 号无菌特氟隆导管将细菌接种到膀胱中。已经评估了单一噬菌体和噬菌体鸡尾酒制剂在经尿道注射两种泌尿道致病性 8 和 302 分离株诱导的慢性 UTI 小鼠模型中的治疗活性。在建立慢性 UTI 小鼠模型 10 天后经尿道和腹腔注射噬菌体的结果显示,单一噬菌体 PEC80 对 UTI 治疗无效,而噬菌体鸡尾酒制剂的两种给药途径均导致给药后 24 小时从小鼠尿液以及牺牲小鼠的膀胱和肾脏匀浆中清除细菌。与噬菌体 PEC80 非常狭窄的宿主范围相比,噬菌体鸡尾酒制剂在治疗慢性 UTI 小鼠模型中的高活性归因于其更广泛的宿主范围。总之,使用噬菌体制剂作为本研究中评估的 25 种噬菌体鸡尾酒进行噬菌体治疗是一种非常有前途和潜在的人类 UTI 替代治疗方法。

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