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Medientyp:
E-Artikel
Titel:
Effects of Endogenous d -Alanine Synthesis and Autoinhibition of Bacillus anthracis Germination on In Vitro and In Vivo Infections
Beteiligte:
McKevitt, Matthew T.;
Bryant, Katie M.;
Shakir, Salika M.;
Larabee, Jason L.;
Blanke, Steven R.;
Lovchik, Julie;
Lyons, C. Rick;
Ballard, Jimmy D.
Erschienen:
American Society for Microbiology, 2007
Beschreibung:
<jats:title>ABSTRACT</jats:title>
<jats:p>
<jats:italic>Bacillus anthracis</jats:italic>
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
<jats:italic>B. anthracis</jats:italic>
survives or succumbs to responsive macrophages. In the current study experiments determined the contribution of endogenous
<jats:sc>d</jats:sc>
-alanine production to the efficiency and timing of
<jats:italic>B. anthracis</jats:italic>
spore germination under in vitro and in vivo conditions. Racemase-mediated production of endogenous
<jats:sc>d</jats:sc>
-alanine by
<jats:italic>B. anthracis</jats:italic>
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
<jats:sc>d</jats:sc>
-alanine production, was prevented by an alanine racemase inhibitor, and required
<jats:sc>l</jats:sc>
-alanine. Interestingly, endogenous production of inhibitory levels of
<jats:sc>d</jats:sc>
-alanine was detected under experimental conditions that did not support germination and in a germination-deficient mutant of
<jats:italic>B. anthracis</jats:italic>
. Racemase-dependent production of
<jats:sc>d</jats:sc>
-alanine enhanced survival of
<jats:italic>B. anthracis</jats:italic>
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
<jats:italic>B. anthracis</jats:italic>
spores administered in the presence of
<jats:sc>d</jats:sc>
-alanine, indicating that rates of germination may be directly influenced by the levels of this amino acid during early stages of disease.
</jats:p>