Affiliation:
1. Department of Microbiology and Molecular Genetics, The University Texas Health Science Center—Houston Medical School, Houston, Texas, USA
Abstract
ABSTRACT
Transcription of the
Bacillus anthracis
structural genes for the anthrax toxin proteins and biosynthetic operon for capsule is positively regulated by AtxA, a transcription regulator with unique properties. Consistent with the role of
atxA
in virulence factor expression, a
B. anthracis atxA
-null mutant is avirulent in a murine model for anthrax. In culture, multiple signals impact
atxA
transcript levels, and the timing and steady-state level of
atxA
expression are critical for optimal toxin and capsule synthesis. Despite the apparent complex control of
atxA
transcription, only one
trans
-acting protein, the transition state regulator AbrB, has been demonstrated to interact directly with the
atxA
promoter. Here we employ 5′ and 3′ deletion analysis and site-directed mutagenesis of the
atxA
control region to demonstrate that
atxA
transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase. We also show that an additional
trans
-acting protein(s) binds specifically to
atxA
promoter sequences located between −13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold. Site-directed mutagenesis of a 9-bp palindromic sequence within the region prevents binding of the
trans
-acting protein(s), increasing promoter activity 7-fold and resulting in a corresponding increase in AtxA and anthrax toxin production. Notably, an
atxA
promoter mutant that produced elevated levels of AtxA and toxin proteins during culture was unaffected for virulence in a murine model for anthrax.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
19 articles.
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