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.
Highlights
1.1 Antimicrobial resistanceAntibiotics are used to treat bacterial infections, by interfering with the growth or other essential mechanisms for survival of the bacteria
Whilst the development of new antibiotics is a possibility for treating these resistant bacteria, the discovery of new antibiotics has slowed within the twenty first century, with the possibility of a post antibiotic era in the coming years (Alanis 2005)
With the ever growing threat of antibiotic resistance, multi drug resistance (MDR) Salmonella have been listed as a high priority for which new treatment methods are required (WHO 2017)
Summary
Antibiotics are used to treat bacterial infections, by interfering with the growth or other essential mechanisms for survival of the bacteria. These essential mechanisms can include maintaining the structure of the cell envelope, protein production and DNA replication (Sköld 2011). Enterobacterales resistant to carbapenem and cephalosporin were classified as critical for the development of new antibiotics. This is a large group of Gram-negative bacteria, which includes Salmonella spp. and Escherichia coli. Salmonella spp. is a genus of rod shaped Gram-negative pathogenic bacteria that is one of the main causes of intestinal infections from food, most commonly from poultry products. High mortality rates are highly prominent in developing countries in these regions, due to poor sanitation and the high prevalence of immunodeficiency diseases (Rowe et al 1997)
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