Chaudhry Waqas Nasir, Concepción-Acevedo Jeniffer, Park Taehyun, Andleeb Saadia, Bull James J, Levin Bruce R
National University of Sciences and Technology, Islamabad, Pakistan.
Department of Biology, Emory University, Atlanta, Georgia, United States of America.
PLoS One. 2017 Jan 11;12(1):e0168615. doi: 10.1371/journal.pone.0168615. eCollection 2017.
In contrast to planktonic cells, bacteria imbedded biofilms are notoriously refractory to treatment by antibiotics or bacteriophage (phage) used alone. Given that the mechanisms of killing differ profoundly between drugs and phages, an obvious question is whether killing is improved by combining antibiotic and phage therapy. However, this question has only recently begun to be explored. Here, in vitro biofilm populations of Pseudomonas aeruginosa PA14 were treated singly and with combinations of two phages and bactericidal antibiotics of five classes. By themselves, phages and drugs commonly had only modest effects in killing the bacteria. However some phage-drug combinations reduced bacterial densities to well below that of the best single treatment; in some cases, bacterial densities were reduced even below the level expected if both agents killed independently of each other (synergy). Furthermore, there was a profound order effect in some cases: treatment with phages before drugs achieved maximum killing. Combined treatment was particularly effective in killing in Pseudomonas biofilms grown on layers of cultured epithelial cells. Phages were also capable of limiting the extent to which minority populations of bacteria resistant to the treating antibiotic ascend. The potential of combined antibiotic and phage treatment of biofilm infections is discussed as a realistic way to evaluate and establish the use of bacteriophage for the treatment of humans.
与浮游细胞不同，嵌入生物膜中的细菌极难被单独使用的抗生素或噬菌体（phage）治疗。鉴于药物和噬菌体的杀伤机制有很大差异，一个显而易见的问题是，联合使用抗生素和噬菌体疗法是否能提高杀菌效果。然而，这个问题直到最近才开始被探索。在这里，对铜绿假单胞菌PA14的体外生物膜群体进行了单独处理，以及用两种噬菌体与五类杀菌抗生素的组合进行处理。噬菌体和药物单独使用时，通常对杀灭细菌的效果有限。然而，一些噬菌体 - 药物组合可将细菌密度降低到远低于最佳单一治疗的水平；在某些情况下，细菌密度甚至降低到低于两种药物相互独立作用时预期的水平（协同作用）。此外，在某些情况下存在显著的顺序效应：先用噬菌体治疗再用药物可达到最大杀菌效果。联合治疗在杀灭培养的上皮细胞层上生长的铜绿假单胞菌生物膜方面特别有效。噬菌体还能够限制对治疗抗生素耐药的少数细菌群体上升的程度。本文讨论了联合抗生素和噬菌体治疗生物膜感染的潜力，认为这是评估和确立噬菌体用于人类治疗的一种切实可行的方法。
