Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA.
Department of Biology, Emory University, Atlanta, GA 30307, USA.
Viruses. 2019 Nov 21;11(12):1083. doi: 10.3390/v11121083.
Phage therapy is the use of bacterial viruses (phages) to treat bacterial infections, a medical intervention long abandoned in the West but now experiencing a revival. Currently, therapeutic phages are often chosen based on limited criteria, sometimes merely an ability to plate on the pathogenic bacterium. Better treatment might result from an informed choice of phages. Here we consider whether phages used to treat the bacterial infection in a patient may specifically evolve to improve treatment on that patient or benefit subsequent patients. With mathematical and computational models, we explore in vivo evolution for four phage properties expected to influence therapeutic success: generalized phage growth, phage decay rate, excreted enzymes to degrade protective bacterial layers, and growth on resistant bacteria. Within-host phage evolution is strongly aligned with treatment success for phage decay rate but only partially aligned for phage growth rate and growth on resistant bacteria. Excreted enzymes are mostly not selected for treatment success. Even when evolution and treatment success are aligned, evolution may not be rapid enough to keep pace with bacterial evolution for maximum benefit. An informed use of phages is invariably superior to naive reliance on within-host evolution.
噬菌体疗法是利用细菌病毒（噬菌体）来治疗细菌感染，这是一种在西方早已被摒弃但现在正在复兴的医学干预手段。目前，治疗性噬菌体的选择通常基于有限的标准，有时仅仅是能够在致病菌上形成菌斑。如果能够明智地选择噬菌体，可能会产生更好的治疗效果。在这里，我们考虑了用于治疗患者细菌感染的噬菌体是否可能专门进化以改善该患者的治疗效果或使后续患者受益。我们使用数学和计算模型，针对可能影响治疗成功的四种噬菌体特性，探索了体内进化：噬菌体的普遍生长、噬菌体的衰减率、分泌的酶来降解保护性细菌层以及在耐药细菌上的生长。噬菌体在体内的进化与噬菌体衰减率的治疗成功率密切相关，但与噬菌体生长率和在耐药细菌上的生长率的治疗成功率只有部分相关。分泌的酶大多没有被选择用于治疗成功率。即使进化和治疗成功率一致，进化也可能不够快，无法跟上细菌进化的速度，从而无法获得最大的益处。明智地使用噬菌体始终优于盲目依赖于体内进化。
