Abstract
Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F2) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study.
Highlights
Bacillus anthracis, the causative agent of anthrax, is a highly virulent pathogen that has been used in recent history as a biological weapon [1]
When compared to bacteria that were grown in iron replete conditions, significant changes in gene expression were observed as early as 2 hours post-inoculation
B. anthracis to low iron concentrations, a signal that mimics conditions encountered by the bacterium within a mammalian host
Summary
The causative agent of anthrax, is a highly virulent pathogen that has been used in recent history as a biological weapon [1]. Our laboratory has previously shown that the macrophage environment in which B. anthracis exists during early infection induces significant transcriptional changes in the bacterium, presumably altering the protein profiles of the organism for optimal growth in this environment [6]. Many pathogens undergo significant changes in their gene and protein expression to adapt to growth in iron limiting conditions, including Francisella tularensis, Mycobacterium tuberculosis, and Streptococcus pneumoniae [12,13,14].
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