HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 16, 12112-12118, April 20, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/16/12112    most recent M611432200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Akoachere, M. Articles by Abel-Santos, E. Search for Related Content PubMed PubMed Citation Articles by Akoachere, M. Articles by Abel-Santos, E. Social Bookmarking                      What's this?

Identification of an in Vivo Inhibitor of Bacillus anthracis Spore Germination^*

Monique Akoachere¹, Raynal C. Squires², Adel M. Nour, Ludmyl Angelov^¶, Jürgen Brojatsch³, and Ernesto Abel-Santos⁴

From the Department of Chemistry, University of Nevada-Las Vegas, Las Vegas, Nevada 89154 and the Departments of Microbiology and Immunology, and ^¶Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461

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.

Received for publication, December 13, 2006 , and in revised form, January 26, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be 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 Award in Global Infectious Diseases and by Public Health Service Grant 1R01AIGM053212 from the National Institute of Health.

² Supported by Grant AI057158 from the Northeast Biodefense Center-Lipkin.

³ To whom correspondence may be addressed: Dept. of Microbiology and Immunology, Albert Einstein College of Medicine, Golding 404, 1300 Morris Park Ave., Bronx, NY 10461. Tel.: 718-430-3079; Fax: 718-430-8711; E-mail: brojatsc{at}aecom.yu.edu. ⁴ To whom correspondence may be addressed: Dept. of Chemistry, University of Nevada-Las Vegas, 4505 Maryland Pkwy., Box 454003, Las Vegas, NV 89154. Tel.: 702-895-2608; Fax: 702-895-4072; E-mail: ernesto.abelsantos{at}unlv.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. K. Cote, J. Bozue, N. Twenhafel, and S. L. Welkos Effects of altering the germination potential of Bacillus anthracis spores by exogenous means in a mouse model J. Med. Microbiol., June 1, 2009; 58(6): 816 - 825. [Abstract] [Full Text] [PDF]

				M. A. Crawford, Y. Zhu, C. S. Green, M. D. Burdick, P. Sanz, F. Alem, A. D. O'Brien, B. Mehrad, R. M. Strieter, and M. A. Hughes Antimicrobial Effects of Interferon-Inducible CXC Chemokines against Bacillus anthracis Spores and Bacilli Infect. Immun., April 1, 2009; 77(4): 1664 - 1678. [Abstract] [Full Text] [PDF]

				J. A. Sorg and A. L. Sonenshein Chenodeoxycholate Is an Inhibitor of Clostridium difficile Spore Germination J. Bacteriol., February 1, 2009; 191(3): 1115 - 1117. [Abstract] [Full Text] [PDF]

				G. Christie and C. R. Lowe Amino Acid Substitutions in Transmembrane Domains 9 and 10 of GerVB That Affect the Germination Properties of Bacillus megaterium Spores J. Bacteriol., December 15, 2008; 190(24): 8009 - 8017. [Abstract] [Full Text] [PDF]

				J. A. Sorg and A. L. Sonenshein Bile Salts and Glycine as Cogerminants for Clostridium difficile Spores J. Bacteriol., April 1, 2008; 190(7): 2505 - 2512. [Abstract] [Full Text] [PDF]

				G. Christie, M. Lazarevska, and C. R. Lowe Functional Consequences of Amino Acid Substitutions to GerVB, a Component of the Bacillus megaterium Spore Germinant Receptor J. Bacteriol., March 15, 2008; 190(6): 2014 - 2022. [Abstract] [Full Text] [PDF]

				M. T. McKevitt, K. M. Bryant, S. M. Shakir, J. L. Larabee, S. R. Blanke, J. Lovchik, C. R. Lyons, and J. D. Ballard Effects of Endogenous D-Alanine Synthesis and Autoinhibition of Bacillus anthracis Germination on In Vitro and In Vivo Infections Infect. Immun., December 1, 2007; 75(12): 5726 - 5734. [Abstract] [Full Text] [PDF]