From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the "cross-over" strain G9241.

G9241 was isolated from a Louisiana welder suffering from an anthrax-like infection. The organism carries two transcriptional regulators that have previously been proposed to be incompatible with each other in : the pleiotropic transcriptional regulator PlcR found in most members of the group but truncated in all isolates, and the anthrax toxin regulator AtxA found in all strains and a few strains. Here we report cytotoxic and hemolytic activity of cell free G9241 culture supernatants cultured at 25°C to various eukaryotic cells. However, this is not observed at the mammalian infection relevant temperature 37°C, behaving much like the supernatants generated by . Using a combination of genetic and proteomic approaches to understand this unique phenotype, we identified several PlcR-regulated toxins to be secreted highly at 25°C compared to 37°C. Furthermore, results suggest that differential expression of the protease involved in processing the PlcR quorum sensing activator molecule PapR appears to be the limiting step for the production of PlcR-regulated toxins at 37°C, giving rise to the temperature-dependent hemolytic and cytotoxic activity of the culture supernatants. This study provides an insight on how G9241 is able to "switch" between and -like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.