Pseudotyping Bacteriophage P2 Tail Fibers to Extend the Host Range for Biomedical Applications.
Pseudotyping Bacteriophage P2 Tail Fibers to Extend the Host Range for Biomedical Applications.
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DOI：
10.1021/acssynbio.1c00629
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发表时间：
2022-10-21
影响因子：
4.7
通讯作者：
Jaramillo, Alfonso
中科院分区：
文献类型：
--
作者：
Cunliffe, Tabitha G.;Parker, Alan L.;Jaramillo, Alfonso
噬菌体（Bacteriophages，简称BPHs）是一种具有强大潜力的抗耐药性细菌感染的治疗手段。抗生素耐药性细菌对全球健康构成重大威胁，估计70%的感染性细菌对一种或多种抗生素具有耐药性。针对有限数量的细胞靶点开发新型抗生素既昂贵又耗时，而且细菌会迅速产生耐药性。虽然细菌对噬菌体的抗性可以进化，但细菌对噬菌体的抗性似乎不会通过横向基因转移传播，并且噬菌体可以类似地通过突变来适应以恢复感染性。噬菌体已被确定为所有已知的细菌，允许菌株选择性杀死病原菌。在这里，我们重新设计了大肠杆菌噬菌体P2，以改变其对病原菌的嗜性。P2和S16基因之间形成的嵌合尾纤维通过两种方法设计和产生：同源性和文献为基础的。通过在P2颗粒上呈现嵌合P2：S16纤维，我们的数据表明，所得的p2p有效地从天然P2细胞靶标脂多糖脱靶，而是能够通过蛋白质受体OmpC（天然S16受体）感染。我们的工作提供的证据表明，假型P2是可行的，并可用于扩展主机范围的P2替代受体。这项工作的扩展可以产生替代的嵌合尾纤维，以靶向致病性细菌的威胁。我们的工程P2允许吸附通过异源外膜蛋白，而无需在其天然宿主中培养，从而提供了一种潜在的手段，从其表面蛋白质组的知识工程设计师对病原菌的抗菌。
Bacteriophages (phages) represent powerful potential treatments against antibiotic-resistant bacterial infections. Antibiotic-resistant bacteria represent a significant threat to global health, with an estimated 70% of infection-causing bacteria being resistant to one or more antibiotics. Developing novel antibiotics against the limited number of cellular targets is expensive and time-consuming, and bacteria can rapidly develop resistance. While bacterial resistance to phage can evolve, bacterial resistance to phage does not appear to spread through lateral gene transfer, and phage may similarly adapt through mutation to recover infectivity. Phages have been identified for all known bacteria, allowing the strain-selective killing of pathogenic bacteria. Here, we re-engineered the Escherichia coli phage P2 to alter its tropism toward pathogenic bacteria. Chimeric tail fibers formed between P2 and S16 genes were designed and generated through two approaches: homology- and literature-based. By presenting chimeric P2:S16 fibers on the P2 particle, our data suggests that the resultant phages were effectively detargeted from the native P2 cellular target, lipopolysaccharide, and were instead able to infect via the proteinaceous receptor, OmpC, the natural S16 receptor. Our work provides evidence that pseudotyping P2 is feasible and can be used to extend the host range of P2 to alternative receptors. Extension of this work could produce alternative chimeric tail fibers to target pathogenic bacterial threats. Our engineering of P2 allows adsorption through a heterologous outer-membrane protein without culturing in its native host, thus providing a potential means of engineering designer phages against pathogenic bacteria from knowledge of their surface proteome.
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DOI：
10.4161/bact.18778
发表时间：
2012-01-01
期刊：
Bacteriophage
影响因子：
--
作者：
Marinelli LJ;Hatfull GF;Piuri M
通讯作者：
Piuri M
影响因子：
4.7
作者：
Grigonyte, Aurelija M.;Harrison, Christian;Millard, Andrew
通讯作者：
Millard, Andrew
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
DOI：
10.3390/antibiotics7030066
发表时间：
2018-07-27
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
--
作者：
Domingo-Calap P;Delgado-Martínez J
通讯作者：
Delgado-Martínez J
影响因子：
9.3
作者：
Ando, Hiroki;Lemire, Sebastien;Lu, Timothy K.
通讯作者：
Lu, Timothy K.