The acetate switch of an intestinal pathogen disrupts host insulin signaling and lipid metabolism

Cell Host Microbe. 2014 Nov 12;16(5):592-604. doi: 10.1016/j.chom.2014.10.006. Epub 2014 Nov 12.


Vibrio cholerae is lethal to the model host Drosophila melanogaster through mechanisms not solely attributable to cholera toxin. To examine additional virulence determinants, we performed a genetic screen in V. cholerae-infected Drosophila and identified the two-component system CrbRS. CrbRS controls transcriptional activation of acetyl-CoA synthase-1 (ACS-1) and thus regulates the acetate switch, in which bacteria transition from excretion to assimilation of environmental acetate. The resultant loss of intestinal acetate leads to deactivation of host insulin signaling and lipid accumulation in enterocytes, resulting in host lethality. These metabolic effects are not observed upon infection with ΔcrbS or Δacs1 V. cholerae mutants. Additionally, uninfected flies lacking intestinal commensals, which supply short chain fatty acids (SCFAs) such as acetate, also exhibit altered insulin signaling and intestinal steatosis, which is reversed upon acetate supplementation. Thus, acetate consumption by V. cholerae alters host metabolism, and dietary acetate supplementation may ameliorate some sequelae of cholera.

Publication types

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

MeSH terms

  • Acetates / metabolism*
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cholera Toxin / toxicity
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / microbiology
  • Enterocytes / metabolism
  • Host-Pathogen Interactions*
  • Immunity, Innate
  • Insulins / metabolism*
  • Intestines / microbiology*
  • Lipid Metabolism*
  • Microbiota
  • Signal Transduction
  • Vibrio cholerae / pathogenicity*
  • Virulence Factors


  • Acetates
  • Bacterial Proteins
  • Insulins
  • Virulence Factors
  • Cholera Toxin
  • Coenzyme A Ligases
  • Acsl1 protein, rat