中文摘要:细菌转导颗粒是分子生物学早期进展的关键,目前正在诊断和治疗领域复苏。但很难开发出一种强大而特异的转导试剂,给构成特定细菌种或属的菌株的多样性提供遗传有效载荷,这极大地阻碍了它们的商业用途。虽然这些试剂的反应工程的最新进展使其对产品开发更具吸引力,但仍需要相当大的改进。本文展示了一个从噬菌体P1衍生的合成生物学平台,作为靶向转导试剂对抗肠杆菌目中四种临床流行的物种的底盘。噬菌体P1只需要一个单一的受体结合蛋白来附着和注射到目标细菌。通过工程和筛选多种嵌合受体结合蛋白的颗粒,生成了一种潜在的转导试剂,用于未来表型碳青霉烯耐药肠杆菌的快速诊断分析。
外文摘要:Bacterial transduction particles were critical to early advances in molecular biology and are currently experiencing a resurgence in interest within the diagnostic and therapeutic fields. The difficulty of developing a robust and specific transduction reagent capable of delivering a genetic payload to the diversity of strains constituting a given bacterial species or genus is a major impediment to their expanded utility as commercial products. While recent advances in engineering the reactivity of these reagents have made them more attractive for product development, considerable improvements are still needed. Here, we demonstrate a synthetic biology platform derived from bacteriophage P1 as a chassis to target transduction reagents against four clinically prevalent species within the Enterobacterales order. Bacteriophage P1 requires only a single receptor binding protein to enable attachment and injection into a target bacterium. By engineering and screening particles displaying a diverse array of chimeric receptor binding proteins, we generated a potential transduction reagent for a future rapid phenotypic carbapenem-resistant Enterobacterales diagnostic assay.
外文关键词:Smarticles;antimicrobial resistance;carbapenem-resistant Enterobacterales;antimicrobial susceptibility testing;synthetic biology;bacteriophage
作者:Lam, CN;Mehta-Kolte, MG;Martins-Sorenson, N;Eckert, B;Lin, PH;Chu, K;Moghaddasi, A;Goldman, D;Nguyen, H;Chan, RY;Nukala, L;Suko, S;Hanson, B;Yuan, R;Cady, KC
作者单位:Roche Mol Syst
期刊名称:ACS SYNTHETIC BIOLOGY
期刊影响因子:4.411
出版年份:2021
出版刊次:6
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