Antibiotic resistance represents a global health challenge. The emergence of multidrug-resistant (MDR) bacteria such as uropathogenic Escherichia coli (UPEC) has attracted significant attention due to increased MDR properties, even against the last line of antibiotics. Bacteriophage, or simply phage, represents an alternative treatment to antibiotics. However, phage applications still face some challenges, such as host range specificity and development of phage resistant mutants. In this study, using both UPEC and non-UPEC hosts, five different phages were isolated from wastewater. We found that the inclusion of commensal Escherichia coli as target hosts during screening improved the capacity to select phage with desirable characteristics for phage therapy. Whole-genome sequencing revealed that four out of five phages adopt strictly lytic lifestyles and are taxonomically related to different phage families belonging to the Myoviridae and Podoviridae. In comparison to single phage treatment, the application of phage cocktails targeting different cell surface receptors significantly enhanced the suppression of UPEC hosts. The emergence of phage-resistant mutants after single phage treatment was attributed to mutational changes in outer membrane protein components, suggesting the potential receptors recognized by these phages. The findings highlight the use of commensal E. coli as target hosts to isolate broad host range phage with infectivity against MDR bacteria.

中文翻译：

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从非目标细菌中分离出的噬菌体对多重耐药菌表现出广泛的宿主范围感染性

抗生素耐药性是一项全球健康挑战。多药耐药 (MDR) 细菌如尿路致病性大肠杆菌(UPEC) 的出现引起了极大的关注，因为它具有增加的 MDR 特性，甚至对抗最后一行抗生素。噬菌体，或简称噬菌体，代表了抗生素的替代疗法。然而，噬菌体应用仍面临一些挑战，例如宿主范围特异性和噬菌体抗性突变体的开发。在这项研究中，使用 UPEC 和非 UPEC 宿主，从废水中分离出五种不同的噬菌体。我们发现包含共生大肠杆菌在筛选过程中作为目标宿主提高了选择具有所需特征的噬菌体进行噬菌体治疗的能力。全基因组测序显示，五分之四的噬菌体采用严格的裂解生活方式，并且在分类学上与属于Myoviridae和Podoviridae 的不同噬菌体家族相关。与单噬菌体处理相比，针对不同细胞表面受体的噬菌体混合物的应用显着增强了对 UPEC 宿主的抑制。单噬菌体处理后出现噬菌体抗性突变体归因于外膜蛋白成分的突变变化，表明这些噬菌体识别的潜在受体。研究结果突出了共生E的使用。大肠杆菌 作为目标宿主以分离对 MDR 细菌具有感染性的广泛宿主范围的噬菌体。