Dysbiosis individualizes fitness effect of antibiotic resistance in the mammalian gut

The fitness cost of antibiotic resistance in the absence of antibiotics is crucial to the success of suspending antibiotics as a strategy to lower resistance. Here we show that after antibiotic treatment the cost of resistance within the complex ecosystem of the mammalian gut is personalized. Using mice as an in vivo model, we find that the fitness effect of the same resistant mutation can be deleterious in a host, but neutral or even beneficial in other hosts. Such antagonistic pleiotropy is shaped by the microbiota, as in germ-free mice resistance is consistently costly across all hosts and in hosts with similar microbiotas the host specific effect of resistance is reduced. An eco-evolutionary model of competition for resources identifies a general mechanism underlying between host variation and predicts that the dynamics of compensatory evolution of resistant bacteria should be host specific, a prediction that was supported by experimental evolution in vivo. The microbiome of each hu...

在无抗生素条件下，抗生素耐药性的适合度成本（fitness cost），对于以停用抗生素作为降低耐药性策略的成败至关重要。本研究表明，抗生素治疗后，哺乳动物肠道复杂生态系统内的耐药性成本存在宿主特异性。本研究以小鼠为体内（in vivo）模型，发现同一耐药突变的适合度效应在某一宿主中可表现为有害性，而在其他宿主中则呈中性甚至有益性。这种拮抗多效性（antagonistic pleiotropy）由宿主微生物群（microbiota）塑造：在无菌小鼠（germ-free mice）中，耐药性在所有宿主中均始终存在适合度成本；而在微生物群相似的宿主中，耐药性的宿主特异性效应会有所减弱。一项基于资源竞争的生态进化模型，揭示了宿主间变异背后的通用机制，并预测耐药细菌的补偿进化动态应具有宿主特异性，这一预测得到了体内（in vivo）实验进化研究的支持。每个宿主的微生物群……