AUTHOR=Manoharan Shathviga , Taylor-Joyce Grace , Brooker Thomas A. , Hernández Rodríguez Carmen Sara , Hapeshi Alexia , Baldwin Victoria , Baillie Les , Oyston Petra C. F. , Waterfield Nicholas R. 

TITLE=From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1113562

DOI=10.3389/fmicb.2023.1113562

ISSN=1664-302X

ABSTRACT=<p><italic>Bacillus cereus</italic> 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 <italic>Bacillus anthracis</italic>: the pleiotropic transcriptional regulator PlcR found in most members of the <italic>Bacillus cereus</italic> group but truncated in all <italic>B. anthracis</italic> isolates, and the anthrax toxin regulator AtxA found in all <italic>B. anthracis</italic> strains and a few <italic>B. cereus sensu stricto</italic> strains. Here we report cytotoxic and hemolytic activity of cell free <italic>B. cereus</italic> 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 <italic>B. anthracis</italic>. 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 <italic>B. cereus</italic> G9241 is able to “switch” between <italic>B. cereus</italic> and <italic>B. anthracis</italic>–like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.</p>