Torres-Barceló Clara, Arias-Sánchez Flor I, Vasse Marie, Ramsayer Johan, Kaltz Oliver, Hochberg Michael E
Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France.
Institut des Sciences de l'Evolution, CNRS-Université Montpellier 2, Montpellier, France; Santa Fe Institute, Santa Fe, New Mexico, United States of America; Wissenshaftskolleg zu Berlin, Berlin, Germany.
PLoS One. 2014 Sep 26;9(9):e106628. doi: 10.1371/journal.pone.0106628. eCollection 2014.
The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.
细菌对抗生素耐药性的演变是一个全球关注的问题，单独使用噬菌体或在联合治疗中使用噬菌体作为一种替代方法正受到越来越多的关注。进化理论预测，细菌对噬菌体和抗生素同时产生耐药性的可能性将低于对两者单独产生耐药性的可能性，例如，这是由于适应度成本或噬菌体耐药机制与细菌生长之间的权衡。在本研究中，我们评估了噬菌体和链霉素单独或联合处理对医院病原体铜绿假单胞菌的群体影响。我们表明，与单独使用相比，噬菌体和抗生素联合使用可显著增强对细菌的控制，并且在不考虑抗生素剂量的情况下，抗生素引入存在特定的时间延迟，这可将细菌密度以及对抗生素或噬菌体的耐药性降至最低。这些结果对最佳联合治疗方法具有启示意义。
