Inhibition of Bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensing

J Infect Dis. 2005 Jun 1;191(11):1881-8. doi: 10.1086/429696. Epub 2005 Apr 29.

Abstract

Density-dependent gene expression, quorum sensing (QS), involves the synthesis and detection of low-molecular-weight molecules known as autoinducers. Inhibitors of bacterial QS systems offer potential treatment of infections with highly virulent or multidrug-resistant agents. We studied the effects on Bacillus anthracis growth and the virulence gene (pagA, lef, and cya) expression of the QS inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is naturally synthesized by the marine alga Delisea pulchra, as well as a related compound and synthetic derivatives. Growth of B. anthracis Sterne strain was substantially reduced in the presence of each furanone in a dose-dependent manner. When furanones were added to midlog-phase cultures of B. anthracis strains with LacZ reporters in pagA, lef, or cya, growth was inhibited, and expression of these virulence genes was inhibited to a proportionately greater extent. These data suggest that use of QS inhibitors could represent novel therapies for anthrax.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacillus anthracis / drug effects*
  • Bacillus anthracis / growth & development*
  • Bacillus anthracis / pathogenicity
  • Bacterial Proteins / metabolism
  • Furans / chemistry
  • Furans / pharmacology*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Molecular Structure
  • Time Factors
  • Virulence / genetics

Substances

  • 4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Furans