Phage therapy revisited: The population biology of a bacterial infection and its treatment with bacteriophage and antibiotics
Phage therapy revisited: The population biology of a bacterial infection and its treatment with bacteriophage and antibiotics
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DOI：
10.1086/285884
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发表时间：
1996-06-01
影响因子：
2.9
通讯作者：
Bull, JJ
中科院分区：
文献类型：
--
作者：
Levin, BR;Bull, JJ
噬菌体疗法是使用细菌病毒（噬菌体）来治疗细菌感染。它已经在人类和家畜身上零星地实践了近75年。尽管如此，噬菌体疗法仍然处于现代医学的主流之外，可能是因为对其疗效的怀疑，也可能是因为它被抗生素和其他化疗药物所掩盖。在这份报告中，我们将噬菌体治疗和抗生素治疗作为一种群体生物学现象进行研究，即细菌与宿主体内的捕食者（噬菌体）或有毒化学物质（抗生素）的动态相互作用，宿主的免疫和其他防御也会影响这种相互作用。我们的目标是确定噬菌体和抗生素可以成功控制细菌感染的条件，以及它们不能成功控制细菌感染的条件。我们回顾了H.威廉姆斯史密斯和J. B。Huggins关于使用噬菌体和抗生素控制实验接种小鼠中大肠杆菌的致死性全身感染。我们表明，他们的一些观察结果可以容纳一个定量模型，调用已知的或合理的假设宿主防御和细菌与噬菌体和抗生素的相互作用;一些观察结果仍然无法解释的模型。我们的分析确定了几个关于噬菌体和抗生素治疗的群体动力学的假设，这些假设可以通过实验进行验证。其中包括解释史密斯和哈金斯使用的不同抗生素疗效差异的假设，以及为什么在他们的研究中，抗生素比抗生素更有效。
Phage therapy is the use of bacterial viruses (bacteriophage) to treat bacterial infections. It has been practiced sporadically on humans and domestic animals for nearly 75 yr. Nevertheless, phage therapy has remained outside the mainstream of modern medicine, presumably because of doubts about its efficacy, and possibly because it was eclipsed by antibiotics and other chemotherapeutic agents. In this report, we develop the study of phage therapy and antibiotic therapy as a population biological phenomenon-the dynamic interaction of bacteria with a predator (phage) or a toxic chemical (antibiotic) inside a host whose immune and other defenses also affect the interaction. Our goal is to identify the conditions under which phage and antibiotics can successfully control a bacterial infection and when they cannot. We review data published in the 1980s by H. Williams Smith and J. B. Huggins on the use of phage and antibiotics to control lethal, systemic infections of Escherichia coli in experimentally inoculated mice. We show that some of their observations can be accommodated by a quantitative model that invokes known or plausible assumptions about host defenses and the interactions of bacteria with phage and antibiotics; some observations remain unexplained by the model. Our analysis identifies several hypotheses about the population dynamics of phage and antibiotic therapy that can be tested experimentally. Included among these are hypotheses that account for variation in the efficacy of the different phages employed by Smith and Huggins and why, in their study, phages were more effective than antibiotics.