Inhibition of Bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensing.
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.
Jones
Marcus B
MB
Department of Microbiology, Sackler Institute, and Department of Medicine, New York University School of Medicine, New York, New York 10016, USA. jonesm02@med.nyu.edu
Jani
Rachana
R
Ren
Dacheng
D
Wood
Thomas K
TK
Blaser
Martin J
MJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000187:drug effects* / Q000254:growth & development* / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000378:metabolism; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D015394:Molecular Structure; D013997:Time Factors; D014774:Virulence / Q000235:genetics
C454202:4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D005663:Furans