Overcoming the phage replication threshold: a mathematical model with implications for phage therapy
Overcoming the phage replication threshold: a mathematical model with implications for phage therapy
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DOI：
10.1128/jvi.76.11.5557-5564.2002
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发表时间：
2002-06-01
影响因子：
5.4
通讯作者：
Norris, JS
中科院分区：
文献类型：
--
作者：
Kasman, LM;Kasman, A;Norris, JS
先前在体外对噬菌体-宿主系统的观察得出结论，在噬菌体复制发生之前，易感宿主细胞群必须达到临界密度。这样的复制阈值密度将对噬菌体的治疗用途产生广泛的影响。在本报告中，我们通过实验证明不存在这样的复制阈值，并根据溶液中胶体粒子相互作用的经典动力学模型解释了先前用于支持阈值存在的数据。这一结果使我们得出结论，通常使用的感染多重性（MOI）测量方法，即噬菌体数量与细胞数量之比，通常不适用于细胞浓度低于10(7)/ml的情况。在它的地方，我们提出了一个替代措施，MOIactual，考虑到细胞浓度和吸附时间。阐明了该函数的性质，解释了MOI在高细胞密度下的实用性，以及在低浓度下的一些意想不到的后果。此外，MOIactual的概念允许我们编写简单的公式来计算实际数量，例如在任意浓度下足以感染99.99%宿主细胞的噬菌体数量。
Prior observations of phage-host systems in vitro have led to the conclusion that susceptible host cell populations must reach a critical density before phage replication can occur. Such a replication threshold density would have broad implications for the therapeutic use of phage. In this report, we demonstrate experimentally that no such replication threshold exists and explain the previous data used to support the existence of the threshold in terms of a classical model of the kinetics of colloidal particle interactions in solution. This result leads us to conclude that the frequently used measure of multiplicity of infection (MOI), computed as the ratio of the number of phage to the number of cells, is generally inappropriate for situations in which cell concentrations are less than 10(7)/ml. In its place, we propose an alternative measure, MOIactual, that takes into account the cell concentration and adsorption time. Properties of this function are elucidated that explain the demonstrated usefulness of MOI at high cell densities, as well as some unexpected consequences at low concentrations. In addition, the concept of MOIactual allows us to write simple formulas for computing practical quantities, such as the number of phage sufficient to infect 99.99% of host cells at arbitrary concentrations.