In Salmonella enterica, the sirtuin-dependent protein acylation/deacylation system (SDPADS) maintains energy homeostasis during growth on low concentrations of acetate

Mol Microbiol. 2011 Apr;80(1):168-83. doi: 10.1111/j.1365-2958.2011.07566.x. Epub 2011 Feb 24.


Acetyl-coenzyme A synthetase (Acs) activates acetate into acetyl-coenzyme A (Ac-CoA) in most cells. In Salmonella enterica, acs expression and Acs activity are controlled. It is unclear why the sirtuin-dependent protein acylation/deacylation system (SDPADS) controls the activity of Acs. Here we show that, during growth on 10 mM acetate, acs(+) induction in a S. enterica strain that cannot acetylate (i.e. inactivate) Acs leads to growth arrest, a condition that correlates with a drop in energy charge (0.17) in the acetylation-deficient strain, relative to the energy charge in the acetylation-proficient strain (0.71). Growth arrest was caused by elevated Acs activity, a conclusion supported by the isolation of a single-amino-acid variant (Acs(G266S)), whose overproduction did not arrest growth. Acs-dependent depletion of ATP, coupled with the rise in AMP levels, prevented the synthesis of ADP needed to replenish the pool of ATP. Consistent with this idea, overproduction of ADP-forming Ac-CoA-synthesizing systems did not affect the growth behaviour of acetylation-deficient or acetylation-proficient strains. The Acs(G266S) variant was >2 orders of magnitude less efficient than the Acs(WT) enzyme, but still supported growth on 10 mM acetate. This work provides the first evidence that SDPADS function helps cells maintain energy homeostasis during growth on acetate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetate-CoA Ligase / genetics
  • Acetate-CoA Ligase / metabolism
  • Acetates / metabolism*
  • Adenosine Triphosphate / metabolism
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Isocitrate Dehydrogenase / metabolism
  • Mutagenesis, Site-Directed
  • Salmonella enterica / genetics
  • Salmonella enterica / metabolism*
  • Sirtuins / metabolism*


  • Acetates
  • Adenosine Triphosphate
  • Isocitrate Dehydrogenase
  • Sirtuins
  • Acetate-CoA Ligase