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

Robin Wray,Irene Iscla,Paul Blount

doi:10.1371/journal.ppat.1010198

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.

Highlights

Curcumin is a flavonoid polyphenol isolated from the rhizome of turmeric (Curcuma longa) and has been shown to have possible therapeutic potential in treatment of cancer and inflammation, and has substantial antibacterial properties [1]
It has been observed that curcumin can lead to bacterial cells that can grow but not divide, leading to long filamentous cells with multiple copies of their DNA
We show that curcumin targets a specific protein in the bacterial cell envelope that can open a very large pore—the largest regulated pore known in the biological world

Summary

Introduction

Curcumin is a flavonoid polyphenol isolated from the rhizome of turmeric (Curcuma longa) and has been shown to have possible therapeutic potential in treatment of cancer and inflammation, and has substantial antibacterial properties [1] It has excellent therapeutic potentials and has been found to be safe and well-tolerated up to a dose as high as 12 g/day without toxicity in clinical trials. Leakage and permeabilization are the most widely described mechanism of action of curcumin as an antibiotic agent [5] This permeabilization appears to be detrimental to the cell for many bacterial species, and the resulting increased cytoplasmic entry of other antibiotics may be a major mechanism for the antibacterial synergy often observed. This effect has been reported for multiple bacterial species, the exact mechanism of curcumin “increased membrane permeabilization”, which is specific for bacterial membranes, remains unknown

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