title: Discriminating virulence mechanisms among Bacillus anthracis strains by using a murine subcutaneous infection model.
abstract: Bacillus anthracis strains harboring virulence plasmid pXO1 that encodes the toxin protein protective antigen (PA), lethal factor, and edema factor and virulence plasmid pXO2 that encodes capsule biosynthetic enzymes exhibit different levels of virulence in certain animal models. In the murine model of pulmonary infection, B. anthracis virulence was capsule dependent but toxin independent. We examined the role of toxins in subcutaneous (s.c.) infections using two different genetically complete (pXO1(+) pXO2(+)) strains of B. anthracis, strains Ames and UT500. Similar to findings for the pulmonary model, toxin was not required for infection by the Ames strain, because the 50% lethal dose (LD(50)) of a PA-deficient (PA(-)) Ames mutant was identical to that of the parent Ames strain. However, PA was required for efficient s.c. infection by the UT500 strain, because the s.c. LD(50) of a UT500 PA(-) mutant was 10,000-fold higher than the LD(50) of the parent UT500 strain. This difference between the Ames strain and the UT500 strain could not be attributed to differences in spore coat properties or the rate of germination, because s.c. inoculation with the capsulated bacillus forms also required toxin synthesis by the UT500 strain to cause lethal infection. The toxin-dependent phenotype of the UT500 strain was host phagocyte dependent, because eliminating Gr-1(+) phagocytes restored virulence to the UT500 PA(-) mutant. These experiments demonstrate that the dominant virulence factors used to establish infection by B. anthracis depend on the route of inoculation and the bacterial strain.
authors.affiliation: Center for Infectious Diseases and Immunity, Department of Pathology, MSC11 6020, University of New Mexico, Albuquerque, NM 87131-0001, USA. hschand@salud.unm.edu
authors.forename: Hitendra S
authors.initials: HS
authors.lastname: Chand
authors.forename: Melissa
authors.initials: M
authors.lastname: Drysdale
authors.forename: Julie
authors.initials: J
authors.lastname: Lovchik
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koehler
authors.forename: Mary F
authors.initials: MF
authors.lastname: Lipscomb
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
mesh_terms: D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000473:pathology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000502:physiology; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000235:genetics; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D037521:Virulence Factors; C030325:anthrax toxin