{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:45:21Z","timestamp":1787701521761,"version":"build-2784847793"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Bacillus cereus<\/jats: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 <jats:italic>Bacillus anthracis<\/jats:italic>: the pleiotropic transcriptional regulator PlcR found in most members of the <jats:italic>Bacillus cereus<\/jats:italic> group but truncated in all <jats:italic>B. anthracis<\/jats:italic> isolates, and the anthrax toxin regulator AtxA found in all <jats:italic>B. anthracis<\/jats:italic> strains and a few <jats:italic>B. cereus sensu stricto<\/jats:italic> strains. Here we report cytotoxic and hemolytic activity of cell free <jats:italic>B. cereus<\/jats:italic> G9241 culture supernatants cultured at 25\u00b0C to various eukaryotic cells. However, this is not observed at the mammalian infection relevant temperature 37\u00b0C, behaving much like the supernatants generated by <jats:italic>B. anthracis<\/jats: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\u00b0C compared to 37\u00b0C. 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\u00b0C, giving rise to the temperature-dependent hemolytic and cytotoxic activity of the culture supernatants. This study provides an insight on how <jats:italic>B. cereus<\/jats:italic> G9241 is able to \u201cswitch\u201d between <jats:italic>B. cereus<\/jats:italic> and <jats:italic>B. anthracis<\/jats:italic>\u2013like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1113562","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T05:29:00Z","timestamp":1677734940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the \u201ccross-over\u201d strain Bacillus cereus G9241"],"prefix":"10.3389","volume":"14","author":[{"given":"Shathviga","family":"Manoharan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Taylor-Joyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Brooker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Sara","family":"Hern\u00e1ndez Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Hapeshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Les","family":"Baillie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra C. F.","family":"Oyston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Waterfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1046\/j.1365-2958.1999.01419.x","article-title":"PlcR is a pleiotropic regulator of extracellular virulence factor gene expression in Bacillus thuringiensis","volume":"32","author":"Agaisse","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0004923","volume":"10","author":"Antonation","year":"2016","journal-title":"PLoS Negl. Trop. 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Mortal. Wkly Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"18490","DOI":"10.1073\/pnas.0704501104","article-title":"Structure of PlcR: insights into virulence regulation and evolution of quorum sensing in gram-positive bacteria","volume":"104","author":"Declerck","year":"2007","journal-title":"PNAS"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/jam.14114","article-title":"Analysis of a newly discovered antigen of Bacillus cereus biovar anthracis for its suitability in specific serological antibody testing","volume":"126","author":"Dupke","year":"2019","journal-title":"J. Appl. Microbiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1128\/JB.00702-06","article-title":"Control of enterotoxin gene expression in Bacillus cereus F4430\/73 involves the redox-sensitive ResDE signal transduction system","volume":"188","author":"Duport","year":"2006","journal-title":"J. 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[Internet]."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"6591","DOI":"10.1128\/IAI.71.11.6591-6606.2003","article-title":"Phosphatidylcholine-specific phospholipase C and sphingomyelinase activities in bacteria of the Bacillus cereus group","volume":"71","author":"Pomerantsev","year":"2003","journal-title":"Infect. Immun."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1111\/j.1574-695X.2008.00521.x","article-title":"PapR peptide maturation: role ofthe NprB protease in Bacillus cereus 569 PlcR \/ PapR global gene regulation","volume":"55","author":"Pomerantsev","year":"2009","journal-title":"FEMS Immunol. Med. 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