Data from: Exposure to phages has little impact on the evolution of bacterial antibiotic resistance on drug concentration gradients

The use of phages for treating bacterial pathogens has recently been advocated as an alternative to antibiotic therapy. Here we test a hypothesis that bacteria treated with phages may show more limited evolution of antibiotic resistance as the fitness costs of resistance to phages may add to those of antibiotic resistance, further reducing the growth performance of antibiotic-resistant bacteria. We did this by studying the evolution of phage-exposed and phage-free Pseudomonas fluorescens cultures on concentration gradients of single drugs, including cefotaxime, chloramphenicol, and kanamycin. During drug treatment, the level of bacterial antibiotic resistance increased through time, and was not affected by the phage treatment. Exposure to phages did not cause slower growth in antibiotic-resistant bacteria, although it did so in antibiotic-susceptible bacteria. We observed significant reversion of antibiotic resistance after drug use being terminated, and the rate of reversion was not affected by the phage treatment. The results suggest that the fitness costs caused by resistance to phages are unlikely to be an important constraint on the evolution of bacterial antibiotic resistance in heterogeneous drug environments. Further studies are needed for the interaction of fitness costs of antibiotic resistance with other factors.

利用噬菌体(phage)治疗细菌性病原体，近来被主张作为抗生素治疗的替代方案。本研究检验了一项假说：经噬菌体处理的细菌，其抗生素耐药性进化可能更为有限——因为噬菌体耐药性带来的适合度代价，可能叠加于抗生素耐药性的适合度代价之上，进一步降低抗生素耐药细菌的生长性能。我们通过在头孢噻肟、氯霉素及卡那霉素等单一抗生素的浓度梯度上，研究暴露于噬菌体与未暴露于噬菌体的荧光假单胞菌培养物的进化过程，完成了上述验证。在药物处理期间，细菌的抗生素耐药水平随时间推移逐步升高，且未受噬菌体处理的影响。噬菌体暴露并未导致抗生素耐药细菌的生长速率下降，但会延缓抗生素敏感细菌的生长。我们观察到，药物停用后，抗生素耐药性出现了显著逆转，且该逆转速率未受噬菌体处理的影响。研究结果表明，噬菌体耐药性带来的适合度代价，不太可能成为异质性药物环境中细菌抗生素耐药性进化的重要约束因素。未来仍需开展进一步研究，以阐明抗生素耐药性的适合度代价与其他因素之间的相互作用。