Transcriptional Profiling of Bacillus anthracisduring Infection of Host Macrophages

Autor: Bergman, Nicholas H., Anderson, Erica C., Swenson, Ellen E., Janes, Brian K., Fisher, Nathan, Niemeyer, Matthew M., Miyoshi, Amy D., Hanna, Philip C.
Zdroj: Infection and Immunity; July 2007, Vol. 75 Issue: 7 p3434-3444, 11p
Abstrakt: ABSTRACTThe interaction between Bacillus anthracisand the mammalian phagocyte is one of the central stages in the progression of inhalational anthrax, and it is commonly believed that the host cell plays a key role in facilitating germination and dissemination of inhaled B. anthracisspores. Given this, a detailed definition of the survival strategies used by B. anthraciswithin the phagocyte is critical for our understanding of anthrax. In this study, we report the first genome-wide analysis of B. anthracisgene expression during infection of host phagocytes. We developed a technique for specific isolation of bacterial RNA from within infected murine macrophages, and we used custom B. anthracismicroarrays to characterize the expression patterns occurring within intracellular bacteria throughout infection of the host phagocyte. We found that B. anthracisadapts very quickly to the intracellular environment, and our analyses identified metabolic pathways that appear to be important to the bacterium during intracellular growth, as well as individual genes that show significant induction in vivo. We used quantitative reverse transcription-PCR to verify that the expression trends that we observed by microarray analysis were valid, and we chose one gene (GBAA1941, encoding a putative transcriptional regulator) for further characterization. A deletion strain missing this gene showed no phenotype in vitro but was significantly attenuated in a mouse model of inhalational anthrax, suggesting that the microarray data described here provide not only the first comprehensive view of how B. anthracissurvives within the host cell but also a number of promising leads for further research in anthrax.
Databáze: Supplemental Index