The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages.
The habits of highly effective phages: population dynamics as a framework for identifying therapeutic phages.
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DOI：
10.3389/fmicb.2014.00618
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发表时间：
2014
影响因子：
5.2
通讯作者：
Gill JJ
中科院分区：
文献类型：
--
作者：
Bull JJ;Gill JJ
噬菌体作为抗菌剂的用途正在全球范围内积极研究。通常，使用的细菌是通过在感兴趣的细菌上铺板从野生环境中分离的，并且通常可获得比可用于任何应用中的大得多的候选细菌集合。当有多余的可供选择的产品时，应如何确定最佳的可供选择产品？在这里，我们认为噬菌体细菌种群动力学作为评估和预测噬菌体成功的基础。一个中心问题是，是否先天的动力学性质的成功的决定因素，或者相反，是否外部的，间接的影响可以负责。我们提出了动态的观点，部分原因是之前提出的噬菌体治疗原则缺乏动态性。目前的细菌噬菌体动力学的数学模型并没有捕捉到体内动力学的现实，也不可能改变，但它们确实提供了可以推广的定性特性的见解。特别是，噬菌体吸附率可能是治疗成功的关键，因此了解体内环境对宿主可用性的影响可能允许在体内实验之前预测有用的噬菌体。预测疗效的原则可以通过对体内系统的更深入理解来推导，或者可以通过比较其动态特性的已知差异来经验性地确定这些原则。比较方法有望成为发现噬菌体成功关键的有力方法。我们为未来的研究提供了五个建议：（i）比较不同的治疗效果，以确定与成功相关的噬菌体特性，（ii）体内测定动力学，（iii）了解细菌从噬菌体逃逸的机制，（iv）在与预期临床应用相关的模型感染中测试噬菌体，以及（v）在空间异质性环境中开发新的噬菌体生长模型。
The use of bacteriophages as antibacterial agents is being actively researched on a global scale. Typically, the phages used are isolated from the wild by plating on the bacteria of interest, and a far larger set of candidate phages is often available than can be used in any application. When an excess of phages is available, how should the best phages be identified? Here we consider phage-bacterial population dynamics as a basis for evaluating and predicting phage success. A central question is whether the innate dynamical properties of phages are the determinants of success, or instead, whether extrinsic, indirect effects can be responsible. We address the dynamical perspective, motivated in part by the absence of dynamics in previously suggested principles of phage therapy. Current mathematical models of bacterial-phage dynamics do not capture the realities of in vivo dynamics, nor is this likely to change, but they do give insight to qualitative properties that may be generalizable. In particular, phage adsorption rate may be critical to treatment success, so understanding the effects of the in vivo environment on host availability may allow prediction of useful phages prior to in vivo experimentation. Principles for predicting efficacy may be derived by developing a greater understanding of the in vivo system, or such principles could be determined empirically by comparing phages with known differences in their dynamic properties. The comparative approach promises to be a powerful method of discovering the key to phage success. We offer five recommendations for future study: (i) compare phages differing in treatment efficacy to identify the phage properties associated with success, (ii) assay dynamics in vivo, (iii) understand mechanisms of bacterial escape from phages, (iv) test phages in model infections that are relevant to the intended clinical applications, and (v) develop new classes of models for phage growth in spatially heterogeneous environments.
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影响因子：
3.7
作者：
Bull, J. J.;Vimr, E. R.;Molineux, I. J.
通讯作者：
Molineux, I. J.
影响因子：
4.2
作者：
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通讯作者：
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影响因子：
3.7
作者：
Chhibber S;Kaur T;Sandeep Kaur
通讯作者：
Sandeep Kaur
影响因子：
4.9
作者：
Bull, J. J.;Otto, G.;Molineux, I. J.
通讯作者：
Molineux, I. J.
DOI：
10.1073/pnas.1305923110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Barr, Jeremy J.;Auro, Rita;Rohwer, Forest
通讯作者：
Rohwer, Forest