中文摘要:抗生素耐药性是一个全球性健康难题。多药耐药(MDR)细菌的出现,如尿路致病性大肠杆菌(UPEC),由于其多药耐药特性的增加,直至最后一种抗生素,已经引起了广泛关注。噬菌体是抗生素的替代物。然而,噬菌体的应用仍然面临一些挑战,如宿主范围特异性和噬菌体耐药突变体的发展。本研究使用UPEC和非UPEC宿主,从废水中分离出5种不同噬菌体。研究发现,筛选过程中将共生大肠杆菌作为目标宿主,可以提高选择具有理想特性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,且在分类上与属于肌病毒科和短尾病毒科的不同噬菌体家族相关。与单一噬菌体治疗相比,针对不同细胞表面受体的噬菌体混合疗法显著增强了对UPEC宿主的抑制。单一噬菌体处理后出现的噬菌体耐药突变体归因于外膜蛋白组分的突变,表明了这些噬菌体识别的潜在受体。该发现强调了利用共生大肠杆菌作为目标宿主来分离对耐多药细菌具有传染性的广泛宿主噬菌体。
外文摘要: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.
外文关键词:SYNONYMOUS CODON USAGE;ESCHERICHIA-COLI;GENE;EVOLUTION
作者:Ngiam, L;Schembri, MA;Weynberg, K;Guo, JH
作者单位:Univ Queensland
期刊名称:ENVIRONMENTAL MICROBIOLOGY
期刊影响因子:4.933
出版年份:2021
出版刊次:
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