Characterization of the Escherichia coli AaeAB Efflux Pump: a Metabolic Relief Valve?

Abstract

Treatment of Escherichia coli with p-hydroxybenzoic acid (pHBA) resulted in upregulation of yhcP, encoding a protein of the putative efflux protein family. Also upregulated were the adjacent genes yhcQ, encoding a protein of the membrane fusion protein family, and yhcR, encoding a small protein without a known or suggested function. The function of the upstream, divergently transcribed gene yhcS, encoding a regulatory protein of the LysR family, in regulating expression of yhcRQP was shown. Furthermore, it was demonstrated that several aromatic carboxylic acid compounds serve as inducers of yhcRQP expression. The efflux function encoded by yhcP was proven by the hypersensitivity to pHBA of a yhcP mutant strain. A yhcS mutant strain was also hypersensitive to pHBA. Expression of yhcQ and yhcP was necessary and sufficient for suppression of the pHBA hypersensitivity of the yhcS mutant. Only a few aromatic carboxylic acids of hundreds of diverse compounds tested were defined as substrates of the YhcQP efflux pump. Thus, we propose renaming yhcS, yhcR, yhcQ, and yhcP, to reflect their role in aromatic carboxylic acid efflux, to aaeR, aaeX, aaeA, and aaeB, respectively. The role of pHBA in normal E. coli metabolism and the highly regulated expression of the AaeAB efflux system suggests that the physiological role may be as a "metabolic relief valve" to alleviate toxic effects of imbalanced metabolism.

Biological activities of lignin hydrolysate-related compounds

“…This can be attributed to the fact that it is a naturally produced metabolite of E. coli and that an efflux pump system exists, i.e., AaeA and AaeB, to push out any excess that may build up within the cell. In fact, it has been reported that the addition of 4-hydroxybenzoic acid exogenously results in the up-regulation of the aaeXAB expression levels which encodes for the putative efflux proteins (55). The authors theorized that this efflux system serves as a metabolic relief valve to reduce the toxicity of the compound.…”

Engineering yeast shikimate pathway towards production of aromatics: rational design of a chassis cell using systems and synthetic biology

“…An active transport of the aromatic out of the cell (Van Dyk et al, 2004) may contribute to achieving these comparatively high titers of extracellular pHBA.…”

“…2 Enumeration of EFMs proceeded at a minimum speed of 3,100 modes/sec when using EFMTool and at an average speed of 50,000 modes/sec when using the new FluxModeCalculator (van Klinken & Willems van Dijk, 2015). NExT reached a minimum speed of 120 modes/sec in case of the most complex S. cerevisiae network when relying on the fmincon solver.…”

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“…It has since been found to be a widespread mechanism in both gram positive and gram negative organisms to expel antibiotics. Efflux pumps also play a major role in extrusion of poorly diffusible endogenous molecules [17,18] and potentially harmful exogenous diffusible substances [19,20] . Resistance nodulation cell division (RND) transporters such as AcrB and its homologues are major multidrug efflux transporters in gram negative bacteria such as E. coli and Pseudomonas aeruginosa [4] .…”