title: Noninvasive imaging technologies reveal edema toxin as a key virulence factor in anthrax.
abstract: Powerful noninvasive imaging technologies enable real-time tracking of pathogen-host interactions in vivo, giving access to previously elusive events. We visualized the interactions between wild-type Bacillus anthracis and its host during a spore infection through bioluminescence imaging coupled with histology. We show that edema toxin plays a central role in virulence in guinea pigs and during inhalational infection in mice. Edema toxin (ET), but not lethal toxin (LT), markedly modified the patterns of bacterial dissemination leading, to apparent direct dissemination to the spleen and provoking apoptosis of lymphoid cells. Each toxin alone provoked particular histological lesions in the spleen. When ET and LT are produced together during infection, a specific temporal pattern of lesion developed, with early lesions typical of LT, followed at a later stage by lesions typical of ET. Our study provides new insights into the complex spatial and temporal effects of B. anthracis toxins in the infected host, suggesting a greater role than previously suspected for ET in anthrax and suggesting that therapeutic targeting of ET contributes to protection.
authors.affiliation: Pathogenesis of Bacterial Toxi-Infections Laboratory, Pasteur Institute (Institut Pasteur), Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Dumetz
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
authors.forename: Huot
authors.initials: H
authors.lastname: Khun
authors.forename: Ian Justin
authors.initials: IJ
authors.lastname: Glomski
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Corre
authors.forename: Clémence
authors.initials: C
authors.lastname: Rougeaux
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Tang
authors.forename: Michèle
authors.initials: M
authors.lastname: Mock
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Pierre Louis
authors.initials: PL
authors.lastname: Goossens
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000473:pathology* / Q000517:prevention & control; D000942:Antigens, Bacterial / Q000276:immunology*; D017209:Apoptosis; D001408:Bacillus anthracis / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000276:immunology*; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006168:Guinea Pigs / Q000382:microbiology; D019570:Inhalation Exposure; D049449:Luminescence; D051379:Mice; D008807:Mice, Inbred BALB C; D009305:Nasopharynx / Q000382:microbiology / Q000473:pathology; D009500:Neutralization Tests; D012867:Skin / Q000382:microbiology / Q000473:pathology; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013997:Time Factors; D037521:Virulence Factors / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D037521:Virulence Factors; C030325:anthrax toxin