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

Bacillus cereus 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 Bacillus anthracis: the pleiotropic transcriptional regulator PlcR found i...

Full description

Bibliographic Details
Main Authors: Shathviga Manoharan, Grace Taylor-Joyce, Thomas A. Brooker, Carmen Sara Hernández Rodríguez, Alexia Hapeshi, Victoria Baldwin, Les Baillie, Petra C. F. Oyston, Nicholas R. Waterfield
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1113562/full
_version_ 1811161701628772352
author Shathviga Manoharan
Grace Taylor-Joyce
Thomas A. Brooker
Carmen Sara Hernández Rodríguez
Alexia Hapeshi
Victoria Baldwin
Les Baillie
Petra C. F. Oyston
Nicholas R. Waterfield
author_facet Shathviga Manoharan
Grace Taylor-Joyce
Thomas A. Brooker
Carmen Sara Hernández Rodríguez
Alexia Hapeshi
Victoria Baldwin
Les Baillie
Petra C. F. Oyston
Nicholas R. Waterfield
author_sort Shathviga Manoharan
collection DOAJ
description Bacillus cereus 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 Bacillus anthracis: the pleiotropic transcriptional regulator PlcR found in most members of the Bacillus cereus group but truncated in all B. anthracis isolates, and the anthrax toxin regulator AtxA found in all B. anthracis strains and a few B. cereus sensu stricto strains. Here we report cytotoxic and hemolytic activity of cell free B. cereus 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 B. 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, 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 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.
first_indexed 2024-04-10T06:18:38Z
format Article
id doaj.art-889342c877f447ffb6587e64e220c70f
institution Directory Open Access Journal
issn 1664-302X
language English
last_indexed 2024-04-10T06:18:38Z
publishDate 2023-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj.art-889342c877f447ffb6587e64e220c70f2023-03-02T05:28:44ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-03-011410.3389/fmicb.2023.11135621113562From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241Shathviga Manoharan0Grace Taylor-Joyce1Thomas A. Brooker2Carmen Sara Hernández Rodríguez3Alexia Hapeshi4Victoria Baldwin5Les Baillie6Petra C. F. Oyston7Nicholas R. Waterfield8Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United KingdomDivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United KingdomDivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United KingdomDpto. Microbiología y Ecología, Instituto BIOTECMED, Universitat de València, Burjassot, SpainDivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United KingdomCBR Division, Dstl Porton Down, Salisbury, United KingdomSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United KingdomCBR Division, Dstl Porton Down, Salisbury, United KingdomDivision of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United KingdomBacillus cereus 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 Bacillus anthracis: the pleiotropic transcriptional regulator PlcR found in most members of the Bacillus cereus group but truncated in all B. anthracis isolates, and the anthrax toxin regulator AtxA found in all B. anthracis strains and a few B. cereus sensu stricto strains. Here we report cytotoxic and hemolytic activity of cell free B. cereus 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 B. 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, 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 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.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1113562/fullBacillus cereus G9241PlcR regulonvirulence factorssecretomehemolysin
spellingShingle Shathviga Manoharan
Grace Taylor-Joyce
Thomas A. Brooker
Carmen Sara Hernández Rodríguez
Alexia Hapeshi
Victoria Baldwin
Les Baillie
Petra C. F. Oyston
Nicholas R. Waterfield
From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
Frontiers in Microbiology
Bacillus cereus G9241
PlcR regulon
virulence factors
secretome
hemolysin
title From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
title_full From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
title_fullStr From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
title_full_unstemmed From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
title_short From cereus to anthrax and back again: Assessment of the temperature-dependent phenotypic switching in the “cross-over” strain Bacillus cereus G9241
title_sort from cereus to anthrax and back again assessment of the temperature dependent phenotypic switching in the cross over strain bacillus cereus g9241
topic Bacillus cereus G9241
PlcR regulon
virulence factors
secretome
hemolysin
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1113562/full
work_keys_str_mv AT shathvigamanoharan fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT gracetaylorjoyce fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT thomasabrooker fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT carmensarahernandezrodriguez fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT alexiahapeshi fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT victoriabaldwin fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT lesbaillie fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT petracfoyston fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241
AT nicholasrwaterfield fromcereustoanthraxandbackagainassessmentofthetemperaturedependentphenotypicswitchinginthecrossoverstrainbacilluscereusg9241