Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties

PLoS Pathog. 2021 Dec 23;17(12):e1010198. doi: 10.1371/journal.ppat.1010198. eCollection 2021 Dec.

Abstract

Curcumin, a natural compound isolated from the rhizome of turmeric, has been shown to have antibacterial properties. It has several physiological effects on bacteria including an apoptosis-like response involving RecA, membrane permeabilization, inhibiting septation, and it can also work synergistically with other antibiotics. The mechanism by which curcumin permeabilizes the bacterial membrane has been unclear. Most bacterial species contain a Mechanosensitive channel of large conductance, MscL, which serves the function of a biological emergency release valve; these large-pore channels open in response to membrane tension from osmotic shifts and, to avoid cell lysis, allow the release of solutes from the cytoplasm. Here we show that the MscL channel underlies the membrane permeabilization by curcumin as well as its synergistic properties with other antibiotics, by allowing access of antibiotics to the cytoplasm; MscL also appears to have an inhibitory role in septation, which is enhanced when activated by curcumin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism
  • Cell Membrane Permeability / drug effects*
  • Curcumin / pharmacology*
  • Escherichia coli
  • Escherichia coli Proteins / drug effects*
  • Escherichia coli Proteins / metabolism
  • Ion Channels / drug effects*
  • Ion Channels / metabolism

Substances

  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Ion Channels
  • MscL protein, E coli
  • Curcumin