title: Capsule synthesis by Bacillus anthracis is required for dissemination in murine inhalation anthrax.
abstract: Bacillus anthracis, the agent of anthrax, produces a poly-D-glutamic acid capsule that has been implicated in virulence. Many strains missing pXO2 (96 kb), which harbors the capsule biosynthetic operon capBCAD, but carrying pXO1 (182 kb) that harbors the anthrax toxin genes, are attenuated in animal models. Also, noncapsulated strains are readily phagocytosed by macrophage cell lines, whereas capsulated strains are resistant to phagocytosis. We show that a strain carrying both virulence plasmids but deleted specifically for capBCAD is highly attenuated in a mouse model for inhalation anthrax. The parent strain and capsule mutant initiated germination in the lungs, but the capsule mutant did not disseminate to the spleen. A mutant harboring capBCAD but deleted for the cap regulators acpA and acpB was also significantly attenuated, in agreement with the capsule-negative phenotype during in vitro growth. Surprisingly, an acpB mutant, but not an acpA mutant, displayed an elevated LD(50) and reduced ability to disseminate, indicating that acpA and acpB are not true functional homologs and that acpB may play a larger role in virulence than originally suspected.
authors.affiliation: Department of Microbiology and Molecular Genetics, The University of Texas Houston Health Science Center, Houston, TX 77030, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Drysdale
authors.forename: Sara
authors.initials: S
authors.lastname: Heninger
authors.forename: Julie
authors.initials: J
authors.lastname: Hutt
authors.forename: Yahua
authors.initials: Y
authors.lastname: Chen
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koehler
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology*; D001408:Bacillus anthracis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D016667:Bacterial Capsules / Q000096:biosynthesis* / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009876:Operon; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D015996:Survival Rate; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D037521:Virulence Factors