Secretion of d-alanine by Escherichia coli

Microbiology (Reading). 2016 Jul;162(7):1243-1252. doi: 10.1099/mic.0.000305. Epub 2016 May 6.

Abstract

Escherichia coli has an l-alanine export system that protects the cells from toxic accumulation of intracellular l-alanine in the presence of l-alanyl-l-alanine (l-Ala-l-Ala). When a DadA-deficient strain was incubated with 6.0 mM l-Ala-l-Ala, we detected l-alanine and d-alanine using high-performance liquid chromatography (HPLC) analysis at a level of 7.0 mM and 3.0 mM, respectively, after 48 h incubation. Treatment of the culture supernatant with d-amino acid oxidase resulted in the disappearance of a signal corresponding to d-alanine. Additionally, the culture supernatant enabled a d-alanine auxotroph to grow without d-alanine supplementation, confirming that the signal detected by HPLC was authentic d-alanine. Upon introduction of an expression vector harbouring the alanine racemase genes, alr or dadX, the extracellular level of d-alanine increased to 11.5 mM and 8.5 mM, respectively, under similar conditions, suggesting that increased metabolic flow from l-alanine to d-alanine enhanced d-alanine secretion. When high-density DadA-deficient cells preloaded with l-Ala-l-Ala were treated with 20 µM carbonyl cyanide m-chlorophenyl hydrazone (CCCP), secretion of both l-alanine and d-alanine was enhanced ~twofold compared with that in cells without CCCP treatment. In contrast, the ATPase inhibitor dicyclohexylcarbodiimide did not exert such an effect on the l-alanine and d-alanine secretion. Furthermore, inverted membrane vesicles prepared from DadA-deficient cells lacking the l-alanine exporter AlaE accumulated [3H]D-alanine in an energy-dependent manner. This energy-dependent accumulation of [3H]D-alanine was strongly inhibited by CCCP. These results indicate that E. coli has a transport system(s) that exports d-alanine and that this function is most likely modulated by proton electrochemical potential.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors
  • Alanine / chemistry
  • Alanine / metabolism*
  • Alanine Racemase / genetics
  • Biological Transport / genetics
  • Biological Transport / physiology*
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology
  • Chromatography, High Pressure Liquid
  • D-Amino-Acid Oxidase / pharmacology
  • Dicyclohexylcarbodiimide / pharmacology
  • Dipeptides / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*

Substances

  • Dipeptides
  • alanylalanine
  • Dicyclohexylcarbodiimide
  • Carbonyl Cyanide m-Chlorophenyl Hydrazone
  • D-Amino-Acid Oxidase
  • Adenosine Triphosphatases
  • Alanine Racemase
  • Alanine