Manktelow C James, Penkova Elitsa, Scott Lucy, Matthews Andrew C, Raymond Ben
Silwood Park Campus, Imperial College, Ascot, United Kingdom.
Centre for Ecology and Conservation, University of Exeter, Penryn, United Kingdom.
Antimicrob Agents Chemother. 2020 Sep 21;64(10). doi: 10.1128/AAC.01033-20.
The acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been quantified primarily using experiments and a small number of studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect model of infection to compare the fitness costs of antibiotic resistance to those Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, , and a Gram-negative intestinal symbiont, Rifampin resistance in showed fitness costs that were typically elevated although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via derepression of AmpC β-lactamase in resulted in no detectable costs or , while spontaneous resistance to nalidixic acid, and carriage of the IncP plasmid RP4, imposed costs that increased Overall, fitness costs were a poor predictor of fitness costs because of strong genotype-environment interactions throughout this study. Insect infections provide a cheap and accessible means of assessing the fitness consequences of resistance mutations, data that are important for understanding the evolution and spread of resistance. This study emphasizes that the fitness costs imposed by particular mutations or different modes of resistance are extremely variable and that only a subset of these mutations is likely to be prevalent outside the laboratory.
获得抗生素抗性通常会带来适应性代价，即在无药物情况下细菌适应性的降低。这些代价主要通过实验和少数在小鼠身上进行的研究来量化，并且通常认为这些不同的方法是一致的。在此，我们使用感染昆虫模型来比较抗生素抗性的适应性代价与那些实验。实验探究了革兰氏阳性病原体和革兰氏阴性肠道共生菌中多种抗性机制。在中，利福平抗性显示出通常升高的适应性代价，尽管这些代价受到基因型 - 环境相互作用的调节。相比之下，通过去阻遏AmpCβ - 内酰胺酶对头孢噻肟产生抗性在中未导致可检测到的代价，而对萘啶酸的自发抗性以及携带IncP质粒RP4则带来了随增加的代价。总体而言，由于整个研究中存在强烈的基因型 - 环境相互作用，适应性代价是适应性代价的一个较差预测指标。昆虫感染提供了一种廉价且可及的手段来评估抗性突变的适应性后果，这些数据对于理解抗性的进化和传播很重要。这项研究强调，特定突变或不同抗性模式所带来的适应性代价极具变异性，并且这些突变中只有一部分可能在实验室之外普遍存在。
