TY - JOUR
T1 - Inhibition of Bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensing
AU - Jones, Marcus B.
AU - Jani, Rachana
AU - Ren, Dacheng
AU - Wood, Thomas K.
AU - Blaser, Martin J.
N1 - Funding Information:
Financial support: Medical Research Service, Department of Veterans Affairs; Northeast Biodefense Center, National Institute of Allergy and Infectious Diseases Regional Center for Excellence (grant U54 AI057 158); American Association for the Advancement of Science; David and Lucile Packard Foundation; Filomena D’Agostino Foundation; United Negro College Fund/Merck (graduate dissertation fellowship).
PY - 2005/6/1
Y1 - 2005/6/1
N2 - 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.
AB - 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.
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U2 - 10.1086/429696
DO - 10.1086/429696
M3 - Article
C2 - 15871122
AN - SCOPUS:18944393301
SN - 0022-1899
VL - 191
SP - 1881
EP - 1888
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 11
ER -