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Effects of Sequential and Simultaneous Applications of Bacteriophages on Populations of Pseudomonas aeruginosaIn Vitro and in Wax Moth Larvae

机译:噬菌体的顺序和同时应用对铜绿假单胞菌体外和蜡蛾幼虫种群的影响

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Interest in using bacteriophages to treat bacterial infections (phage therapy) is growing, but there have been few experiments comparing the effects of different treatment strategies on both bacterial densities and resistance evolution. While it is established that multiphage therapy is typically more effective than the application of a single phage type, it is not clear if it is best to apply phages simultaneously or sequentially. We tried single- and multiphage therapy against Pseudomonas aeruginosa PAO1 in vitro , using different combinations of phages either simultaneously or sequentially. Across different phage combinations, simultaneous application was consistently equal or superior to sequential application in terms of reducing bacterial population density, and there was no difference (on average) in terms of minimizing resistance. Phage-resistant bacteria emerged in all experimental treatments and incurred significant fitness costs, expressed as reduced growth rate in the absence of phages. Finally, phage therapy increased the life span of wax moth larvae infected with P. aeruginosa , and a phage cocktail was the most effective short-term treatment. When the ratio of phages to bacteria was very high, phage cocktails cured otherwise lethal infections. These results suggest that while adding all available phages simultaneously tends to be the most successful short-term strategy, there are sequential strategies that are equally effective and potentially better over longer time scales.
机译:使用噬菌体治疗细菌感染(噬菌体治疗)的兴趣正在增长,但是很少有实验比较不同治疗策略对细菌密度和耐药性演变的影响。虽然已经确定多噬菌体疗法通常比单一噬菌体类型更有效,但尚不清楚最好同时或顺序使用噬菌体。我们在体外尝试了针对铜绿假单胞菌PAO1的单噬菌体和多噬菌体疗法,同时或顺序使用了不同的噬菌体组合。在不同的噬菌体组合中,就减少细菌种群密度而言,同时应用始终如一地等于或优于顺序应用,并且在最大程度降低抗性方面没有差异(平均)。在所有实验处理中均出现了抗噬菌体细菌,并招致了巨大的适应力成本,表现为在没有噬菌体的情况下生长速度降低。最后,噬菌体疗法可延长感染铜绿假单胞菌的蜡蛾幼虫的寿命,而噬菌体鸡尾酒是最有效的短期治疗方法。当噬菌体与细菌的比例很高时,噬菌体混合物会治愈,否则会造成致命的感染。这些结果表明,虽然同时添加所有可用的噬菌体往往是最成功的短期策略,但有些顺序策略同样有效,并且在更长的时间内可能会更好。

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