Impact of a Novel PagR-like Transcriptional Regulator on Cereulide Toxin Synthesis in Emetic <i>Bacillus cereus</i>

oleh: Eva Maria Kalbhenn, Markus Kranzler, Agnieszka Gacek-Matthews, Gregor Grass, Timo D. Stark, Elrike Frenzel, Monika Ehling-Schulz

Format: Article
Diterbitkan: MDPI AG 2022-09-01

Deskripsi

The emetic type of foodborne disease caused by <i>Bacillus cereus</i> is produced by the small peptide toxin cereulide. The genetic locus encoding the Ces nonribosomal peptide synthetase (CesNRPS) multienzyme machinery is located on a 270 kb megaplasmid, designated pCER270, which shares its backbone with the <i>Bacillus anthracis</i> toxin plasmid pXO1. Although the <i>ces</i> genes are plasmid-borne, the chromosomally encoded pleiotropic transcriptional factors CodY and AbrB are key players in the control of <i>ces</i> transcription. Since these proteins only repress cereulide synthesis during earlier growth phases, other factors must be involved in the strict control of <i>ces</i> expression and its embedment in the bacterial life cycle. <i>In silico</i> genome analysis revealed that pCER270 carries a putative ArsR/SmtB family transcription factor showing high homology to PagR from <i>B. anthracis</i>. As PagR plays a crucial role in the regulation of the protective antigen gene <i>pagA</i>, which forms part of anthrax toxin, we used a gene-inactivation approach, combined with electrophoretic mobility shift assays and a bacterial two-hybrid system for dissecting the role of the PagR homologue PagRBc in the regulation of cereulide synthesis. Our results highlight that the plasmid-encoded transcriptional regulator PagRBc plays an important role in the complex and multilayered process of cereulide synthesis.