Capsules, Toxins and AtxA as Virulence Factors of Emerging Bacillus cereus Biovar anthracis

Autor: Fabian H. Leendertz, Silke R. Klee, Michèle Mock, Jean-Philippe Corre, Tatjana Franz, Susann Dupke, Christophe Brézillon, Angelika Lander, Michel Haustant, Roland Grunow, Grégory Jouvion, Pierre L. Goossens, Evelyne Couture-Tosi, Marc Monot
Přispěvatelé: Pathogénie des Toxi-infections bactériennes, Institut Pasteur [Paris] (IP), Centre for Biological Threats and Special Pathogens [Berlin] (ZBS), Robert Koch Institute [Berlin] (RKI), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Histopathologie humaine et Modèles animaux, Epidemiology of Highly Pathogenic Microorganisms, This work was partly supported by the'Deutsche Forschungsgemeinschaft' (DFG) grant KL 2521/1-1 (RKI) and the InVS (IP)., Institut Pasteur [Paris], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre National de Référence du Charbon-Pathogénie des Toxi-infections bactériennes (CNR)
Rok vydání: 2014
Předmět:
Bacterial capsule
MESH: Bacterial Toxins/genetics
Biovar
Bacillus cereus
MESH: Antigens
Bacterial/genetics
MESH: Bacillus cereus/genetics
Mice
Plasmid
MESH: Animals
MESH: Bacterial Capsules/metabolism
0303 health sciences
MESH: Anthrax/microbiology
biology
Virulence
lcsh:Public aspects of medicine
MESH: Genomics
MESH: Toxins
Biological
MESH: Bacillus cereus/classification
Genomics
3. Good health
Bacillus anthracis
Infectious Diseases
Cereus
Research Article
Plasmids
lcsh:Arctic medicine. Tropical medicine
lcsh:RC955-962
Virulence Factors
Bacterial Toxins
Microbiology
Anthrax
03 medical and health sciences
MESH: Plasmids
MESH: Virulence Factors/genetics
Animals
MESH: Bacterial Toxins/metabolism
MESH: Virulence/genetics
MESH: Mice
Bacterial Capsules
030304 developmental biology
Toxins
Biological
MESH: Bacillus anthracis/metabolism
Antigens
Bacterial
Polyglutamate
MESH: Bacillus anthracis/pathogenicity
030306 microbiology
Public Health
Environmental and Occupational Health
Correction
lcsh:RA1-1270
MESH: Virulence Factors/metabolism
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
biology.organism_classification
Virology
MESH: Bacillus cereus/metabolism
MESH: Bacterial Capsules/genetics
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, 2015, 9 (4), pp.e0003455. ⟨10.1371/journal.pntd.0003455⟩
PLoS Neglected Tropical Diseases, Public Library of Science, 2015, 9 (4), pp.e0003455. ⟨10.1371/journal.pntd.0003455⟩
PLoS Neglected Tropical Diseases, Vol 9, Iss 4, p e0003455 (2015)
ISSN: 1935-2735
1935-2727
DOI: 10.1371/journal.pntd.0003455⟩
Popis: Emerging B. cereus strains that cause anthrax-like disease have been isolated in Cameroon (CA strain) and Côte d’Ivoire (CI strain). These strains are unusual, because their genomic characterisation shows that they belong to the B. cereus species, although they harbour two plasmids, pBCXO1 and pBCXO2, that are highly similar to the pXO1 and pXO2 plasmids of B. anthracis that encode the toxins and the polyglutamate capsule respectively. The virulence factors implicated in the pathogenicity of these B. cereus bv anthracis strains remain to be characterised. We tested their virulence by cutaneous and intranasal delivery in mice and guinea pigs; they were as virulent as wild-type B. anthracis. Unlike as described for pXO2-cured B. anthracis, the CA strain cured of the pBCXO2 plasmid was still highly virulent, showing the existence of other virulence factors. Indeed, these strains concomitantly expressed a hyaluronic acid (HA) capsule and the B. anthracis polyglutamate (PDGA) capsule. The HA capsule was encoded by the hasACB operon on pBCXO1, and its expression was regulated by the global transcription regulator AtxA, which controls anthrax toxins and PDGA capsule in B. anthracis. Thus, the HA and PDGA capsules and toxins were co-regulated by AtxA. We explored the respective effect of the virulence factors on colonisation and dissemination of CA within its host by constructing bioluminescent mutants. Expression of the HA capsule by itself led to local multiplication and, during intranasal infection, to local dissemination to the adjacent brain tissue. Co-expression of either toxins or PDGA capsule with HA capsule enabled systemic dissemination, thus providing a clear evolutionary advantage. Protection against infection by B. cereus bv anthracis required the same vaccination formulation as that used against B. anthracis. Thus, these strains, at the frontier between B. anthracis and B. cereus, provide insight into how the monomorphic B. anthracis may have emerged.
Author Summary Anthrax is caused by the bacterium Bacillus anthracis that affects all mammals worldwide. It emerged more than 10,000 years ago from a Bacillus cereus precursor. In the past decade, B. cereus bacteria were isolated in the USA from anthrax-like pneumonia cases. They harbour one virulence plasmid very similar to the toxin–encoding plasmid of B. anthracis. Recently, an anthrax-like disease in great apes in Africa was caused by emerging B. cereus strains, named B. cereus biovar anthracis. These strains are atypical as they possess both plasmids coding for toxin and capsule similar to those so far found only in B. anthracis. These unusual pathogenic B. cereus are currently neglected. We explored the virulence of these pathogens and their colonisation and dissemination capacity within the murine host. We found that these toxinogenic strains harbour two capsules, the classical B. anthracis capsule and an additional polysaccharidic capsule. This latter capsule confers virulence alone or in combination with toxins. Both capsules are concomitantly expressed, under the control of a common global regulator and host signals. Our results show that acquisition of new genetic information by these B. cereus clearly gives them a selective advantage, favouring their dissemination within infected hosts and the environment.
Databáze: OpenAIRE
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