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

Saiyu Hang1, Alexandra E Purdy1, William P Robins2

  • 1Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

Cell Host & Microbe
|December 20, 2014
PubMed

Insights

Vibrio cholerae virulence involves more than cholera toxin. The CrbRS system and acetate consumption disrupt host insulin signaling and cause lethality in Drosophila, suggesting acetate supplementation as a potential therapy.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • Vibrio cholerae causes lethal cholera through complex mechanisms.
  • Cholera toxin is a known virulence factor, but other determinants are implicated.
  • The model host Drosophila melanogaster is used to study V. cholerae pathogenesis.

Purpose of the Study:

  • To identify novel V. cholerae virulence factors beyond cholera toxin.
  • To elucidate the role of bacterial metabolism in host lethality.
  • To investigate the impact of V. cholerae infection on host metabolic pathways.

Main Methods:

  • Genetic screening of V. cholerae in infected Drosophila melanogaster.
  • Analysis of the two-component system CrbRS and its target acetyl-CoA synthase-1 (ACS-1).
  • Assessment of host insulin signaling, lipid accumulation, and intestinal steatosis.

Main Results:

  • The CrbRS two-component system was identified as a key virulence determinant.
  • CrbRS regulates acetate assimilation by V. cholerae via ACS-1.
  • V. cholerae's consumption of intestinal acetate disrupts host insulin signaling and causes lethal steatosis.
  • Acetate supplementation reversed metabolic alterations in uninfected flies lacking commensals.

Conclusions:

  • Vibrio cholerae utilizes the CrbRS system to manipulate host acetate levels, leading to metabolic disruption and lethality.
  • Bacterial acetate consumption is a significant virulence mechanism in this model.
  • Dietary acetate supplementation may offer a therapeutic strategy against cholera-related metabolic complications.

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