Time dependent asymptotic analysis of the gene regulatory network of the AcrAB-TolC efflux pump system in gram-negative bacteria

Youlden, George H.; Ricci, Vito; Wang-Kan, Xuan; Piddock, Laura J.V.; Jabbari, Sara; King, John R.

Abstract

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.

Citation

Youlden, G. H., Ricci, V., Wang-Kan, X., Piddock, L. J., Jabbari, S., & King, J. R. (2021). Time dependent asymptotic analysis of the gene regulatory network of the AcrAB-TolC efflux pump system in gram-negative bacteria. Journal of Mathematical Biology, 82, Article 31. https://doi.org/10.1007/s00285-021-01576-4

• Journal Article Type: Article
• Acceptance Date: Feb 14, 2021
• Online Publication Date: Mar 10, 2021
• Publication Date: Mar 10, 2021
• Deposit Date: Apr 25, 2021
• Publicly Available Date: Apr 27, 2021
• Journal: Journal of Mathematical Biology
• Print ISSN: 0303-6812
• Electronic ISSN: 1432-1416
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 82
• Article Number: 31
• DOI: https://doi.org/10.1007/s00285-021-01576-4
• Public URL: https://nottingham-repository.worktribe.com/output/5495862
• Publisher URL: https://link.springer.com/article/10.1007/s00285-021-01576-4