The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure

ABSTRACT Bacillus cereus is among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportun...

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Autores principales:	Elrike Frenzel, Markus Kranzler, Timo D. Stark, Thomas Hofmann, Monika Ehling-Schulz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/de4cc78d0dc84815a76e9b0cd3f22c8c
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spelling	oai:doaj.org-article:de4cc78d0dc84815a76e9b0cd3f22c8c2021-11-15T15:41:23ZThe Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure10.1128/mBio.01172-152150-7511https://doaj.org/article/de4cc78d0dc84815a76e9b0cd3f22c8c2015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01172-15https://doaj.org/toc/2150-7511ABSTRACT Bacillus cereus is among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportunistic pathogen is increasingly associated with rapidly fatal clinical infections especially linked to neonates and immunocompromised individuals. Fatality results from either the misdiagnosis of B. cereus as a contaminant of the clinical specimen or from failure of antibiotic therapy. Here we report for the first time that exposure to aminoglycoside antibiotics induces a phenotype switching of emetic B. cereus subpopulations to a slow-growing small colony variant (SCV) state. Along with altered antibiotic resistance, SCVs showed distinct phenotypic and metabolic properties, bearing the risk of antibiotic treatment failure and of clinical misdiagnosis by standard identification tests used in routine diagnostic. The SCV subpopulation is characterized by enhanced production of the toxin cereulide, but it does not secrete tissue-destructive and immune system-affecting enzymes such as sphingomyelinase and phospholipase. SCVs showed significantly prolonged persistence and decreased virulence in the Galleria mellonella model for bacterial infections, indicating diversification concerning their ecological lifestyle. Importantly, diversification into coexisting wild-type and SCV subpopulations also emerged during amikacin pressure during in vivo infection experiments. IMPORTANCE This study shows for the first time that pathogenic spore-forming B. cereus strains are able to switch to a so far unreported slow-growing lifestyle, which differs substantially in terms of developmental, phenotypic, metabolic, and virulence traits from the wild-type populations. This underpins the necessity of molecular-based differential diagnostics and a well-chosen therapeutic treatment strategy in clinical environments to combat B. cereus in a tailored manner. The reported induction of SCV in an endospore-forming human pathogen requires further research to broaden our understanding of a yet unexplored antibiotic resistance mechanism in sporulating bacteria. Our work also raises a general question about the ecological meaning of SCV subpopulation emergence and importance of SCV in sporeformer populations as an alternative route, next to sporulation, to cope with stresses encountered in natural niches, such as soil or host interfaces.Elrike FrenzelMarkus KranzlerTimo D. StarkThomas HofmannMonika Ehling-SchulzAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Elrike Frenzel Markus Kranzler Timo D. Stark Thomas Hofmann Monika Ehling-Schulz The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
description	ABSTRACT Bacillus cereus is among the microorganisms most often isolated from cases of food spoilage and causes gastrointestinal diseases as well as nongastrointestinal infections elicited by the emetic toxin cereulide, enterotoxins, and a panel of tissue-destructive virulence factors. This opportunistic pathogen is increasingly associated with rapidly fatal clinical infections especially linked to neonates and immunocompromised individuals. Fatality results from either the misdiagnosis of B. cereus as a contaminant of the clinical specimen or from failure of antibiotic therapy. Here we report for the first time that exposure to aminoglycoside antibiotics induces a phenotype switching of emetic B. cereus subpopulations to a slow-growing small colony variant (SCV) state. Along with altered antibiotic resistance, SCVs showed distinct phenotypic and metabolic properties, bearing the risk of antibiotic treatment failure and of clinical misdiagnosis by standard identification tests used in routine diagnostic. The SCV subpopulation is characterized by enhanced production of the toxin cereulide, but it does not secrete tissue-destructive and immune system-affecting enzymes such as sphingomyelinase and phospholipase. SCVs showed significantly prolonged persistence and decreased virulence in the Galleria mellonella model for bacterial infections, indicating diversification concerning their ecological lifestyle. Importantly, diversification into coexisting wild-type and SCV subpopulations also emerged during amikacin pressure during in vivo infection experiments. IMPORTANCE This study shows for the first time that pathogenic spore-forming B. cereus strains are able to switch to a so far unreported slow-growing lifestyle, which differs substantially in terms of developmental, phenotypic, metabolic, and virulence traits from the wild-type populations. This underpins the necessity of molecular-based differential diagnostics and a well-chosen therapeutic treatment strategy in clinical environments to combat B. cereus in a tailored manner. The reported induction of SCV in an endospore-forming human pathogen requires further research to broaden our understanding of a yet unexplored antibiotic resistance mechanism in sporulating bacteria. Our work also raises a general question about the ecological meaning of SCV subpopulation emergence and importance of SCV in sporeformer populations as an alternative route, next to sporulation, to cope with stresses encountered in natural niches, such as soil or host interfaces.
format	article
author	Elrike Frenzel Markus Kranzler Timo D. Stark Thomas Hofmann Monika Ehling-Schulz
author_facet	Elrike Frenzel Markus Kranzler Timo D. Stark Thomas Hofmann Monika Ehling-Schulz
author_sort	Elrike Frenzel
title	The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
title_short	The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
title_full	The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
title_fullStr	The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
title_full_unstemmed	The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure
title_sort	endospore-forming pathogen <named-content content-type="genus-species">bacillus cereus</named-content> exploits a small colony variant-based diversification strategy in response to aminoglycoside exposure
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/de4cc78d0dc84815a76e9b0cd3f22c8c
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The Endospore-Forming Pathogen <named-content content-type="genus-species">Bacillus cereus</named-content> Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure

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