**Inhibition ofBacillus anthracisGrowth and Virulence-Gene Expression by Inhibitors of Quorum-Sensing**

Jones, Marcus B
Jani, Rachana
Ren, Dacheng
Wood, Thomas K
Blaser, Martin J

¹Department of Microbiology, Sackler Institute
²Department of Medicine, New York University School of Medicine, and
³Department of Veterans Affairs Medical Center, New York, and
⁴School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York;
⁵Departments of Chemical Engineering and Molecular and Cell Biology, University of Connecticut, Storrs

Reprints or correspondence: Dr. Marcus Jones, Dept. of Microbiology, New York University School of Medicine, 550 First Ave., New York, NY 10016 ([email protected]).

Received 17 September 2004; revised 27 September 2002; accepted 17 December 2004.

Presented in part: American Society for Microbiology General Meeting, New Orleans, 23-27 May 2004 (abstract S5:7); American Society for Microbiology Cell-to-Cell Communication Meeting, Banff, Alberta, Canada, 23-27 July 2004.

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).

Journal of Infectious Diseases 191(11):p 1881-1888, June 1, 2005. | DOI: 10.1086/429696

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 onBacillus anthracisgrowth and the virulence gene (pagA, lefandcya) expression of the QS inhibitor(5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is naturally synthesized by the marine algaDelisea pulchraas well as a related compound and synthetic derivatives. Growth ofB. anthracisSterne strain was substantially reduced in the presence of each furanone in a dose-dependent manner. When furanones were added to midlog-phase cultures ofB. anthracisstrains with LacZ reporters inpagA, leforcyagrowth 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.