Identification of an in Vivo Inhibitor of Bacillus anthracis Spore Germination*
Journal - Journal of Biological Chemistry
Germination of Bacillus anthracis spores into the vegetativeform is an essential step in anthrax pathogenicity. This processcan be triggered in vitro by the common germinants inosine andalanine. Kinetic analysis of B. anthracis spore germinationrevealed synergy and a sequential mechanism between inosineand alanine binding to their cognate receptors. Because inosineis a critical germinant in vitro, we screened inosine analogsfor the ability to block in vitro germination of B. anthracisspores. Seven analogs efficiently blocked this process in vitro.This led to the identification of 6-thioguanosine, which alsoefficiently blocked spore germination in macrophages and preventedkilling of these cells mediated by B. anthracis spores. 6-Thioguanosineshows potential as an anti-anthrax therapeutic agent.* The costs of publication of this article were defrayed in partby the payment of page charges. This article must thereforebe hereby marked "advertisement" in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.1 Supported by the Ellison Medical Foundation Young Scholar Awardin Global Infectious Diseases and by Public Health Service Grant1R01AIGM053212 from the National Institute of Health.2 Supported by Grant AI057158 from the Northeast Biodefense Center-Lipkin.