Bile salts and fatty acids induce the expression of Escherichia coli AcrAB multidrug efflux pump through their interaction with Rob regulatory protein

Mol Microbiol. 2003 Jun;48(6):1609-19. doi: 10.1046/j.1365-2958.2003.03531.x.

Abstract

AcrAB of Escherichia coli, an archetype among bacterial multidrug efflux pumps, exports an extremely wide range of substrates including solvents, dyes, detergents and antimicrobial agents. Its expression is regulated by three XylS/AraC family regulators, MarA, SoxS and Rob. Although MarA and SoxS regulation works by the alteration of their own expression levels, it was not known how Rob, which is constitutively expressed, exerts its regulatory action. We show here that the induction of the AcrAB efflux pump by decanoate and the more lipophilic unconjugated bile salts is mediated by Rob, and that the low-molecular-weight inducers specifically bind to the C-terminal, non-DNA-binding domain of Rob. Induction of Rob is not needed for induction of AcrAB, and we suggest that the inducers act by producing conformational alterations in pre-existing Rob, as was suggested recently (Rosner, Dangi, Gronenborn and Martin, J Bacteriol 184: 1407-1416, 2002). Decanoate and unconjugated bile salts, which are present in the normal habitat of E. coli, were further shown to make the bacteria more resistant to lipophilic antibiotics, at least in part because of the induction of the AcrAB efflux pump. Thus, it is likely that E. coli is protecting itself by the Rob-mediated upregulation of AcrAB against the harmful effects of bile salts and fatty acids in the intestinal tract.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bile Acids and Salts / metabolism
  • Bile Acids and Salts / pharmacology*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Decanoates / pharmacology
  • Drug Resistance, Bacterial
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Fatty Acids / metabolism
  • Fatty Acids / pharmacology*
  • Gene Expression Regulation, Bacterial*
  • Lipoproteins / genetics
  • Lipoproteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins

Substances

  • AcrA protein, E coli
  • AcrB protein, E coli
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bile Acids and Salts
  • Carrier Proteins
  • DNA-Binding Proteins
  • Decanoates
  • Escherichia coli Proteins
  • Fatty Acids
  • Lipoproteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Rob protein, E coli