In Vivo Gene Expression Profiling of the Plague Bacillus, Yersinia Pestis

Yersinia pestis, the causative agent of plague, can be transmitted by infected-flea bite or inhaled aerosol. Both routes of infection have a high mortality rate, and pneumonic infections of Yersinia pestis represent a significant fear as a tool of bioterrorism. Understanding the transcriptional program of this pathogen during pulmonary infection is valuable to better understand plague pathogenesis. Improved understanding of the mechanisms employed by Y. pestis to cause illness may lead to new vaccines or therapies. Using a long-oligonucleotide microarray to the plague bacillus I evaluated the expression profiles of in vitro and in vivo models of Y. pestis. The change in temperature from ambient (e.g. aerosol or flea midgut) to the mammalian host has been used as a model to understand the effects of temperature as a signal for virulence gene expression. I have profiled transcription during an aerosol delivered mouse infection. By amplifying the Y. pestis RNA from individual mouse lungs, I was able to map the transcriptional profile of plague at post-infection days 1 to 3. My data suggest a dramatically altered transcriptional profile relative to the in vitro model, suggesting Y. pestis is responding to a variety of host signals during infection. Of note was the number of genes found in genomic regions with altered %GC content that are up-regulated within the mouse lung environment. These data suggest these regions may provide promising targets for future therapy design and vaccine target discovery.