Weld Richard J, Butts Christine, Heinemann Jack A
School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.
J Theor Biol. 2004 Mar 7;227(1):1-11. doi: 10.1016/S0022-5193(03)00262-5.
Phage therapy is complicated by the self-replicating nature of phage. It is difficult to extrapolate from in vitro phage growth data to in vivo expectations, difficult to interpret in vivo data and difficult to generalize from one in vivo situation to another. Various generic models of phage growth have been used as the theoretical basis for understanding the kinetics of phage therapy. Here, we have experimentally tested the efficacy of such simple models to predict, qualitatively and quantitatively, the growth of phage and the phage proliferation threshold in vitro. Naturally occurring, antibiotic-resistant bacteria were used to measure the growth of phage in vivo. In homogenous, in vitro environments, the models were predictive of T4 phage growth on Escherichia coli RR1. However, the models were not able to predict growth of T4 phage or K1-5 phage in the more complex environment of the rat's digestive tract. To explore fully the kinetics of phage therapy, more complex models need to be devised. We suggest that it may be necessary to consider and model the interactions between phage growth parameters and bacterial growth parameters.
噬菌体疗法因噬菌体的自我复制特性而变得复杂。很难从体外噬菌体生长数据推断体内预期情况，难以解读体内数据，也难以将一种体内情况推广至另一种情况。各种噬菌体生长的通用模型已被用作理解噬菌体治疗动力学的理论基础。在此，我们通过实验测试了此类简单模型在定性和定量预测体外噬菌体生长及噬菌体增殖阈值方面的有效性。利用天然存在的抗生素抗性细菌来测量体内噬菌体的生长。在均匀的体外环境中，这些模型能够预测T4噬菌体在大肠杆菌RR1上的生长。然而，这些模型无法预测T4噬菌体或K1 - 5噬菌体在大鼠消化道这种更复杂环境中的生长。为了全面探索噬菌体治疗的动力学，需要设计更复杂的模型。我们认为可能有必要考虑并模拟噬菌体生长参数与细菌生长参数之间的相互作用。
