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Strong Environment-Genotype Interactions Determine the Fitness Costs of Antibiotic Resistance In Vitro and in an Insect Model of Infection.
Antimicrobial Agents and Chemotherapy ( IF 4.9 ) Pub Date : 2020-09-21 , DOI: 10.1128/aac.01033-20
C James Manktelow 1, 2 , Elitsa Penkova 2 , Lucy Scott 2 , Andrew C Matthews 2 , Ben Raymond 2, 3
Affiliation  

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 in vitro experiments and a small number of in vivo 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 in vivo to those in vitro. Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, Bacillus thuringiensis, and a Gram-negative intestinal symbiont, Enterobacter cloacae. Rifampin resistance in B. thuringiensis showed fitness costs that were typically elevated in vivo, although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via derepression of AmpC β-lactamase in E. cloacae resulted in no detectable costs in vivo or in vitro, while spontaneous resistance to nalidixic acid, and carriage of the IncP plasmid RP4, imposed costs that increased in vivo. Overall, fitness costs in vitro were a poor predictor of fitness costs in vivo 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.

中文翻译:

强烈的环境-基因型相互作用决定了体外和感染昆虫模型中抗生素耐药性的适应性成本。

获得抗生素抗性通常会增加适应性成本,在没有药物的情况下降低细菌的适应性。这些成本主要通过体外实验和小鼠体内的少量体内研究来量化,通常认为这些不同的方法是一致的。在这里,我们使用昆虫感染模型比较了体内体外抗生素耐药性的适应性成本。实验探索了革兰氏阳性病原体苏云金芽孢杆菌和革兰氏阴性肠道共生菌阴沟肠杆菌的耐药机制。苏云金芽孢杆菌对利福平的耐药性研究表明,健身费用通常在体内增加,尽管这些费用受基因型-环境相互作用的调节。相反,在阴沟肠杆菌中通过抑制AmpCβ-内酰胺酶对头孢噻肟的耐药性导致体内体外检测不到成本,而对萘啶酸的自发耐药性和IncP质粒RP4的运输导致体内成本增加。总体而言,体外健身费用不能很好地预测体内健身费用由于整个研究过程中强烈的基因型-环境相互作用。昆虫感染为评估抗药性突变的适应性后果提供了一种廉价且容易获得的方法,这些数据对于理解抗药性的演变和传播非常重要。这项研究强调,特定突变或不同抗性模式所带来的适应性成本变化很大,而且这些突变中只有一部分在实验室外很普遍。
更新日期:2020-09-21
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