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From cereus to anthrax and back again : the role of the PlcR regulator in the “cross-over” strain Bacillus cereus G9241

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Manoharan, Shathviga, Taylor-Joyce, Grace, Brooker, Thomas A., Hernandez-Rodriguez, Carmen Sara, Hapeshi, Alexia, Baldwin, Victoria, Baillie, Les, Oyston, Petra C. F. and Waterfield, Nicholas R. (2022) From cereus to anthrax and back again : the role of the PlcR regulator in the “cross-over” strain Bacillus cereus G9241. Working Paper. BioRxiv. (Submitted)

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Official URL: http://dx.doi.org/10.1101/2022.07.06.498675

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Abstract

The plcR gene, which encodes the pleiotropic transcriptional regulator of secreted proteins found in most members of the Bacillus cereus group, is truncated in all Bacillus anthracis isolates. The current dogma suggests this truncation was evolved to accommodate the acquisition of the anthrax toxin regulator, AtxA. However, the B. cereus-B. anthracis “cross-over” strain Bacillus cereus G9241, isolated from a Louisiana welder suffering from an anthrax-like infection, appears to contradict the proposed dogma as it encodes intact copies of both regulators. Here we report that when cultured at 25 °C, cell free B. cereus G9241 culture supernatants are cytotoxic and haemolytic to various eukaryotic cells in addition to insect haemocytes from Manduca sexta. However, this cytotoxic and haemolytic activity of the culture supernatant is lost when the bacteria are grown at 37 °C, behaving much like the supernatants generated by B. anthracis. Using a combination of genetic and proteomic approaches, we identified several PlcR-regulated toxins secreted at 25 °C. We demonstrate that a limiting step for the production of these virulence factors at 37 °C exists within the PlcR-PapR regulation circuit in strain G9241, giving rise to the temperature-dependent haemolytic and cytotoxic activity of the culture supernatants. Differential expression of the protease responsible in processing the PlcR quorum sensing activator PapR appears to be responsible for this phenotype. This study confirms that B. cereus G9241 is able to ‘switch’ between B. cereus and B. anthracis–like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.

Item Type: Working or Discussion Paper (Working Paper)
Subjects: Q Science > QK Botany
Q Science > QP Physiology
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Bacillus cereus, Secretion -- Regulation , Plants -- Secretion
Publisher: BioRxiv
Official Date: 7 July 2022
Dates:
DateEvent
7 July 2022Published
DOI: 10.1101/2022.07.06.498675
Institution: University of Warwick
Status: Not Peer Reviewed
Publication Status: Submitted
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
DSTLX1000093952Defence Science and Technology Laboratoryhttp://dx.doi.org/10.13039/100010418
DSTLX-1000128995Defence Science and Technology Laboratoryhttp://dx.doi.org/10.13039/100010418
UNSPECIFIED[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
FP7-PEOPLE-2010-IEFMarie Curiehttp://dx.doi.org/10.13039/501100000654
UNSPECIFIEDWarwick Medical Schoolhttp://dx.doi.org/10.13039/501100004443
UNSPECIFIEDCardiff Universityhttp://dx.doi.org/10.13039/501100000866
UNSPECIFIEDDefence Science and Technology Laboratoryhttp://dx.doi.org/10.13039/100010418
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