Department of Zoology, University of Oxford, United Kingdom.
Am Nat. 2010 Sep;176(3):303-11. doi: 10.1086/655217.
Hypermutable (mutator) bacteria have been associated with the emergence of antibiotic resistance. A simple yet untested prediction is that mutator bacteria are able to compensate more quickly for pleiotropic fitness costs often associated with resistance, resulting in the maintenance of resistance in the absence of antibiotic selection. By using experimental populations of a wild-type and a mutator genotype of the pathogenic bacterium Pseudomonas aeruginosa, we show that mutator bacteria can evolve resistance to antibiotics more rapidly than wild-type bacteria and, crucially, that mutators are better able to compensate for the fitness cost of resistance, to the extent that all costs of resistance were entirely compensated for in mutators. When competed against immigrant antibiotic-susceptible bacteria in the absence of antibiotics, antibiotic resistance remained at a high level in mutator populations but disappeared in wild-type populations. These results suggest that selection for mutations that offset the fitness cost associated with antibiotic resistance may help to explain the high frequency of mutator bacteria and antibiotic resistance observed in chronic infections.
高突变（突变型）细菌与抗生素耐药性的出现有关。一个简单但未经检验的预测是，突变型细菌能够更快地补偿通常与耐药性相关的多效性适应代价，从而在没有抗生素选择的情况下维持耐药性。通过使用致病性细菌铜绿假单胞菌的野生型和突变型实验种群，我们表明突变型细菌比野生型细菌更能快速进化出对抗生素的耐药性，而且至关重要的是，突变型细菌能够更好地补偿耐药性的适应代价，以至于所有耐药性的代价在突变型细菌中都完全得到了补偿。当在没有抗生素的情况下与外来的抗生素敏感细菌竞争时，抗生素耐药性在突变型种群中仍然保持在较高水平，但在野生型种群中消失了。这些结果表明，选择能够抵消与抗生素耐药性相关的适应代价的突变可能有助于解释慢性感染中高频率的突变型细菌和抗生素耐药性。
