Exploring the wider roles of TetR-family efflux regulators AcrR and EnvR in E. coli and Salmonella

Colclough, Abigail Lucy (2021). Exploring the wider roles of TetR-family efflux regulators AcrR and EnvR in E. coli and Salmonella. University of Birmingham. Ph.D.

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Abstract

The efflux system AcrAB-TolC extrudes a range of antimicrobials, dyes and detergents in Salmonella Typhimurium. Consequently, the overexpression of the acrAB genes confers multi-drug resistance. The AcrEF-TolC system is believed to extrude some of the same substrates as AcrAB-TolC, but the conditions which induce the expression of acrEF are unknown. Here, induction of acrA and acrE transcription occurred in response to a variety of conditions and substrates of AcrAB, with both acrAB and acrEF being induced by the addition of indole or rhodamine 6g.

The expression of the acrAB genes is negatively regulated by the TetR-family transcription factors AcrR and EnvR, which are local regulators of the acrAB and acrEF efflux genes, respectively. However, EnvR also regulates acrAB, making acrAB a global target of EnvR. Here, AcrR and EnvR protein showed weak binding upstream of multiple, global targets and the overexpression of acrR or envR altered the expression of these target genes. Therefore, AcrR and EnvR may have roles in addition to regulating acrAB. This study also highlights that there is much heterogeneity in the TetR-family of transcription factors found in Salmonella and Escherichia, even between strains of the same species, with many predicted to have multiple gene targets. Therefore, TetR-family transcription factors, including AcrR and EnvR, may have wider regulatory roles than are currently known.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):