The anti-inflammatory drug mesalamine targets bacterial polyphosphate accumulation

Nat Microbiol. 2017 Jan 23;2:16267. doi: 10.1038/nmicrobiol.2016.267.

Abstract

Mesalamine serves as the gold standard in treating ulcerative colitis. However, its precise mechanism(s) of action remains unclear. Here, we show that mesalamine treatment rapidly decreases polyphosphate levels in diverse bacteria, including members of the human gut microbiome. This decrease sensitizes bacteria towards oxidative stress, reduces colonization and attenuates persister cell and biofilm formation, suggesting that mesalamine aids in diminishing the capacity of bacteria to persist within chronically inflamed environments.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biofilms / drug effects
  • Cecum / microbiology
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / microbiology
  • Escherichia coli / drug effects
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / physiology*
  • Humans
  • Mesalamine / administration & dosage
  • Mesalamine / pharmacology*
  • Mesalamine / therapeutic use
  • Mice
  • Oxidative Stress / drug effects
  • Polyphosphates / metabolism*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Polyphosphates
  • Mesalamine