Bacillus anthracis can cause lethal inhalational anthrax and can be used as a bioweapon due to its ability to form spores and to survive under various environmental stress conditions. YhgC in bacilli are structural homologues of TRAP, a protein involved in stress response in staphylococci. To test the role of YhgC in B. anthracis, YhgC gene was deleted in B. anthracis strain Sterne and parent and mutant strains tested. Immunolocalization studies indicated that YhgC is clustered both on the cell surface and within the cytoplasm. Phenotypic analyses indicated that YhgC is an important factor for oxidative stress tolerance and for macrophage infection in vitro. Accordingly, transcriptomics studies indicated that yhgC has a profound effect on genes encoding for stress response regulatory proteins where it negatively regulates the expression of genes encoding for Class I and Class III stress response proteins belonging to the regulons hrcA (hrcA, grpE, dnaK, dnaJ, groEL and groES) and ctsR (ctsR, mcsA, mcsB, clpC/mecB, clpP1). Proteomics studies also indicated that YhgC positively regulates the expression of ClpP-2 and camelysin, which are proteins involved in adaptive responses and pathogenesis in various Gram-positive bacteria. Put together, these results suggest that YhgC is important for the survival of B. anthracis under oxidative stress conditions and thus inhibition of YhgC may compromise the ability of the bacteria to survive within the host.
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