Protein secretion plays a critical role in bacterial pathogenesis; the majority of identified pathogenicity determinants are secreted proteins. The mechanisms for protein secretion are largely uncharacterized in Gram-positive bacteria. Recently a novel secretion factor, SecA2, was identified in several Gram-positive pathogens. SecA2 is involved in secretion of virulence factors in at least four bacterial species and has been observed in the genomes of several other Gram-positive pathogens while being absent in non-pathogens. A homolog of SecA2 has been identified in Bacillus anthracis, the causative agent of anthrax. I will identify secretion substrates of the SecA2 secretion system and determine if they play a role as novel virulence factors in anthrax pathogenesis. Studies will also be conducted to identify the regulatory mechanisms governing expression of SecA2 secreted substrates. Future studies of how these substrates interact with the host will give us a better understanding of host immunity and anthrax disease.
