Fromcereusto anthrax and back again: The role of the PlcR regulator in the “cross-over” strainBacillus cereusG9241

Abstract

ABSTRACTBacillus cereusG9241 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: the pleiotropic transcriptional regulator PlcR found in most members of theBacillus cereusgroup but truncated in allBacillus anthracisisolates, and the anthrax toxin regulator AtxA found in allB. anthracisstrains and a fewB. cereussensu stricto strains. Here we report cytotoxic and haemolytic activity of cell freeB. cereusG9241 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 byB. anthracis. 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, we demonstrate 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 haemolytic and cytotoxic activity of the culture supernatants. This study provides an insight on howB. cereusG9241 is able to ‘switch’ betweenB. cereusandB. anthracis–like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.