Identification of an in vivo inhibitor of Bacillus anthracis spore germination.
Germination of Bacillus anthracis spores into the vegetative form is an essential step in anthrax pathogenicity. This process can be triggered in vitro by the common germinants inosine and alanine. Kinetic analysis of B. anthracis spore germination revealed synergy and a sequential mechanism between inosine and alanine binding to their cognate receptors. Because inosine is a critical germinant in vitro, we screened inosine analogs for the ability to block in vitro germination of B. anthracis spores. Seven analogs efficiently blocked this process in vitro. This led to the identification of 6-thioguanosine, which also efficiently blocked spore germination in macrophages and prevented killing of these cells mediated by B. anthracis spores. 6-Thioguanosine shows potential as an anti-anthrax therapeutic agent.
Akoachere
Monique
M
Department of Chemistry, University of Nevada-Las Vegas, Las Vegas, Nevada 89154, USA.
Squires
Raynal C
RC
Nour
Adel M
AM
Angelov
Ludmyl
L
Brojatsch
Jürgen
J
Abel-Santos
Ernesto
E
D000409:Alanine / Q000737:chemistry; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007288:Inosine / Q000737:chemistry; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D013171:Spores, Bacterial / Q000378:metabolism*; D013872:Thionucleosides / Q000737:chemistry
D000900:Anti-Bacterial Agents; D013872:Thionucleosides; D006151:Guanosine; D007288:Inosine; C005783:6-thioguanosine; D000409:Alanine