Damon W. Ellison, Tina R. Clark, Daniel E. Sturdevant, Kimmo Virtaneva, Ted Hackstadt

Rickettsiae are strict obligate intracellular pathogens that alternate between arthropod and mammalian hosts in a zoonotic cycle. Typically, pathogenic bacteria that cycle between environmental sources and mammalian hosts adapt to the respective environments by coordinately regulating gene expression such that genes essential for survival and virulence are expressed only upon infection of mammals. Temperature is a common environmental signal for upregulation of virulence gene expression although other factors may also play a role. We examined the transcriptional responses of Rickettsia rickettsii, the agent of Rocky Mountain spotted fever, to a variety of environmental signals expected to be encountered during its life cycle. R. rickettsii exposed to differences in growth temperature (25 degrees C vs. 37 degrees C), iron limitation, and host cell species displayed nominal changes in gene expression under any of these conditions with only 0, 5, or 7 genes, respectively, changing more than 3-fold in expression levels. R. rickettsii is not totally devoid of ability to respond to temperature shifts as cold shock (37 degrees C vs. 4 degrees C) induced a change greater than 3-fold in up to 56 genes. Rickettsiae continuously occupy a relatively stable environment which is the cytosol of eukaryotic cells. Because of their obligate intracellular character, rickettsiae are believed to be undergoing reductive evolution to a minimal genome. We propose that their relatively constant environmental niche has led to a minimal requirement for R. rickettsii to respond to environmental changes with a consequent deletion of non-essential transcriptional response regulators. A minimal number of predicted transcriptional regulators in the R. rickettsii genome is consistent with this hypothesis.