Journal of Mathematical Biology ( IF 2.2 ) Pub Date : 2021-03-10 , DOI: 10.1007/s00285-021-01576-4 George H Youlden 1, 2, 3 , Vito Ricci 3 , Xuan Wang-Kan 3, 4 , Laura J V Piddock 3 , Sara Jabbari 1, 3 , John R King 2
Efflux pumps are a mechanism of intrinsic and evolved resistance in bacteria. If an efflux pump can expel an antibiotic so that its concentration within the cell is below a killing threshold the bacteria are resistant to the antibiotic. Efflux pumps may be specific or they may pump various different substances. This is why many efflux pumps confer multi drug resistance (MDR). In particular over expression of the AcrAB−TolC efflux pump system confers MDR in both Salmonella and Escherichia coli. We consider the complex gene regulation network that controls expression of genes central to controlling the efflux associated genes acrAB and acrEF in Salmonella. We present the first mathematical model of this gene regulatory network in the form of a system of ordinary differential equations. Using a time dependent asymptotic analysis, we examine in detail the behaviour of the efflux system on various different timescales. Asymptotic approximations of the steady states provide an analytical comparison of targets for efflux inhibition.
中文翻译:
革兰氏阴性细菌中AcrAB-TolC外排泵系统的基因调控网络的时间依赖性渐近分析
外排泵是细菌内在和进化抵抗力的机制。如果外排泵可以排出抗生素,从而使其在细胞内的浓度低于杀灭阈值,则细菌对抗生素具有抗性。外排泵可能是特定的,也可能会泵送各种不同的物质。这就是为什么许多外排泵都具有多重耐药性(MDR)的原因。特别是AcrAB-TolC外排泵系统的过度表达使沙门氏菌和大肠杆菌中的MDR都升高。我们认为,复杂的基因调控网络的基因,以中央控制外排有关的基因表达控制的acrAB和acrEF在沙门氏菌。我们以常微分方程组的形式介绍了该基因调控网络的第一个数学模型。使用时间相关的渐近分析,我们详细检查了流出系统在各种不同时间尺度上的行为。稳态的渐近近似提供了用于外排抑制的靶标的分析比较。