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

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...

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Vydané v:PLoS neglected tropical diseases Ročník 9; číslo 4; s. e0003455
Hlavní autori: Brézillon, Christophe, Haustant, Michel, Dupke, Susann, Corre, Jean-Philippe, Lander, Angelika, Franz, Tatjana, Monot, Marc, Couture-Tosi, Evelyne, Jouvion, Gregory, Leendertz, Fabian H., Grunow, Roland, Mock, Michèle E., Klee, Silke R., Goossens, Pierre L.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Public Library of Science 01.04.2015
Public Library of Science (PLoS)
Predmet:
Animals
Anthrax - microbiology
Antigens, Bacterial - genetics
Antigens, Bacterial - metabolism
Bacillus anthracis
Bacillus anthracis - genetics
Bacillus anthracis - metabolism
Bacillus anthracis - pathogenicity
Bacillus cereus
Bacillus cereus - classification
Bacillus cereus - genetics
Bacillus cereus - metabolism
Bacterial Capsules - genetics
Bacterial Capsules - metabolism
Bacterial Toxins - genetics
Bacterial Toxins - metabolism
Biochemistry, Molecular Biology
Genes
Genetic aspects
Genomes
Genomics
Life Sciences
Mice
Molecular biology
Mutation
Nosocomial infections
Plasmids
Properties
Regulatory genes
Toxins
Toxins, Biological
Virulence (Microbiology)
Virulence - genetics
Virulence Factors - genetics
Virulence Factors - metabolism
ISSN:1935-2735, 1935-2727, 1935-2735
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Shrnutí: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.
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content type line 23
These authors contributed equally to this work.
Conceived and designed the experiments: SD SRK RG MM PLG CB JPC. Performed the experiments: SD AL TF CB MH JPC MM ECT GJ PLG. Analyzed the data: SD SRK CB JPC MM ECT GJ MEM PLG. Contributed reagents/materials/analysis tools: FHL. Wrote the paper: SD SRK FHL RG CB MM PLG.
The authors have declared that no competing interests exist.
ISSN:1935-2735
1935-2727
1935-2735
DOI:10.1371/journal.pntd.0003455