Effects of Endogenous D-Alanine Synthesis and Autoinhibition of Bacillus anthracis Germination on In Vitro and In Vivo Infections

Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs t...

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Published inInfection and Immunity Vol. 75; no. 12; pp. 5726 - 5734
Main Authors McKevitt, Matthew T, Bryant, Katie M, Shakir, Salika M, Larabee, Jason L, Blanke, Steven R, Lovchik, Julie, Lyons, C. Rick, Ballard, Jimmy D
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.12.2007
American Society for Microbiology (ASM)
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Summary:Bacillus anthracis transitions from a dormant spore to a vegetative bacillus through a series of structural and biochemical changes collectively referred to as germination. The timing of germination is important during early steps in infection and may determine if B. anthracis survives or succumbs to responsive macrophages. In the current study experiments determined the contribution of endogenous D-alanine production to the efficiency and timing of B. anthracis spore germination under in vitro and in vivo conditions. Racemase-mediated production of endogenous D-alanine by B. anthracis altered the kinetics for initiation of germination over a range of spore densities and exhibited a threshold effect wherein small changes in spore number resulted in major changes in germination efficiency. This threshold effect correlated with D-alanine production, was prevented by an alanine racemase inhibitor, and required L-alanine. Interestingly, endogenous production of inhibitory levels of D-alanine was detected under experimental conditions that did not support germination and in a germination-deficient mutant of B. anthracis. Racemase-dependent production of D-alanine enhanced survival of B. anthracis during interaction with murine macrophages, suggesting a role for inhibition of germination during interaction with these cells. Finally, in vivo experiments revealed an approximately twofold decrease in the 50% lethal dose of B. anthracis spores administered in the presence of D-alanine, indicating that rates of germination may be directly influenced by the levels of this amino acid during early stages of disease.
Bibliography:http://iai.asm.org/
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Present address: Department of Genome Sciences, University of Washington, Seattle, WA 98195.
Editor: A. Camilli
Corresponding author. Mailing address: University of Oklahoma Health Sciences Center, BRC-362A, 975 NE 10th Street, Oklahoma City, OK 73104. Phone: (405) 271-3855. Fax: (405) 271-3874. E-mail: jimmy-ballard@ouhsc.edu
ISSN:0019-9567
1098-5522
DOI:10.1128/IAI.00727-07