Lacotte Yohann, Ploy Marie-Cécile, Raherison Sophie
Université de Limoges, INSERM, CHU Limoges, UMR_S 1092, Limoges, France.
ISME J. 2017 Jul;11(7):1535-1544. doi: 10.1038/ismej.2017.38. Epub 2017 Apr 7.
Resistance integrons are bacterial genetic platforms that can capture and express antibiotic resistance genes embedded within gene cassettes. The capture and shuffling of gene cassettes are mediated by the integrase IntI, the expression of which is regulated by the SOS response in Escherichia coli. Gene cassettes are expressed from a common Pc promoter. Despite the clinical and environmental relevance of integrons, the selective forces responsible for their evolution and maintenance are poorly understood. Here, we conducted pairwise competition experiments in order to assess the fitness cost of class 1 integrons in E. coli. We found that integrons are low-cost structures and that their cost is further reduced by their tight regulation. We show that the SOS response prevents the expression of costly integrases whose cost is activity dependent. Thus, when an integron is repressed, its cost depends mostly on the expression of its gene cassettes array and increases with Pc strength and the number of cassettes in the array. Furthermore, different cassettes have different costs. Lastly, we showed that subinhibitory antibiotic concentrations promoted the selection of integron-carrying bacteria, especially those with a strong Pc promoter. These results provide new insights into the evolutionary dynamics of integron-carrying bacterial populations.
抗性整合子是细菌的遗传平台,能够捕获并表达嵌入基因盒中的抗生素抗性基因。基因盒的捕获和重排由整合酶IntI介导,其表达在大肠杆菌中受SOS应答调控。基因盒从共同的Pc启动子进行表达。尽管整合子在临床和环境方面具有相关性,但其进化和维持所涉及的选择压力仍知之甚少。在此,我们进行了成对竞争实验,以评估1类整合子在大肠杆菌中的适应性代价。我们发现整合子是低成本结构,并且通过其严格调控,其代价会进一步降低。我们表明,SOS应答可阻止表达代价高昂的整合酶,其代价取决于活性。因此,当整合子受到抑制时,其代价主要取决于其基因盒阵列的表达,并随着Pc强度和阵列中盒的数量增加而增加。此外,不同的盒具有不同的代价。最后,我们表明亚抑制浓度的抗生素促进了携带整合子细菌的选择,尤其是那些具有强Pc启动子的细菌。这些结果为携带整合子的细菌群体的进化动态提供了新的见解。