Use of bacteriophage to target bacterial surface structures required for virulence: a systematic search for antibiotic alternatives.
Use of bacteriophage to target bacterial surface structures required for virulence: a systematic search for antibiotic alternatives.
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DOI：
10.1007/s00294-016-0603-5
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发表时间：
2016-11
期刊：
影响因子：
2.5
通讯作者：
Orndorff, Paul E.
中科院分区：
文献类型：
--
作者：
Orndorff, Paul E.
感染病原菌的噬菌体（噬菌体）通常附着在表面受体上，这些受体恰好是毒力所需的。通过突变的受体损失或修饰使得突变体减毒和噬菌体抗性。这种减毒突变体通常没有明显的实验室生长缺陷，但在宿主中，它们不能表现出产生疾病所需的性质，如粘膜定植或在专职吞噬细胞内存活。减毒和噬菌体抗性之间的联系已经在噬菌体治疗的实验演示中被利用。在这样的实验中，在治疗过程中自然产生的噬菌体抗性突变体是无关紧要的，因为它们的减毒状态。利用这种联系的更现代的方法涉及鉴定在高通量筛选中鉴定的小效应分子，其抑制产生功能性噬菌体受体所需的一个或多个步骤。由于这种生物合成步骤是细菌独有的，因此可以在治疗上使用抑制剂代替抗生素。此外，由于抑制剂对特定细菌或细菌群具有特异性，因此在宿主的肠道细菌群体中不会产生脱靶耐药性。这篇简短的综述涵盖了赋予噬菌体抗性的突变如何产生衰减的例子，以及如何利用这种巧合的关系来寻找下一代细菌性疾病的治疗药物。
Bacteriophage (phage) that infect pathogenic bacteria often attach to surface receptors that are coincidentally required for virulence. Receptor loss or modification through mutation renders mutants both attenuated and phage resistant. Such attenuated mutants frequently have no apparent laboratory growth defects, but in the host, they fail to exhibit properties needed to produce disease such as mucosal colonization or survival within professional phagocytic cells. The connection between attenuation and phage resistance has been exploited in experimental demonstrations of phage therapy. In such experiments, phage resistant mutants that arise naturally during therapy are inconsequential because of their attenuated status. A more contemporary approach to exploiting this connection involves identifying small effector molecules, identified in high throughput screens, that inhibit one or more of the steps needed to produce a functioning phage receptor. Since such biosynthetic steps are unique to bacteria, inhibitors can be utilized therapeutically, in lieu of antibiotics. Also, since the inhibitor is specific to a particular bacterium or group of bacteria, no off-target resistance is generated in the host’s commensal bacterial population. This brief review covers examples of how mutations that confer phage resistance produce attenuation, and how this coincidental relationship can be exploited in the search for the next generation of therapeutic agents for bacterial diseases.
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影响因子：
5.2
作者：
León M;Bastías R
通讯作者：
Bastías R
影响因子：
3.6
作者：
Eugster, Marcel R.;Haug, Martina C.;Loessner, Martin J.
通讯作者：
Loessner, Martin J.
DOI：
10.1073/pnas.1209126109
发表时间：
2012-11-13
影响因子：
11.1
作者：
Brown, Stephanie;Xia, Guoqing;Walker, Suzanne
通讯作者：
Walker, Suzanne
DOI：
10.1001/jama.1934.72750500003009
发表时间：
1934-07-01
影响因子：
--
作者：
Eaton, MD;Bayne-Jones, S
通讯作者：
Bayne-Jones, S
影响因子：
5.6
作者：
Fourches D;Muratov E;Ding F;Dokholyan NV;Tropsha A
通讯作者：
Tropsha A