Toxin-deficient mutants of Bacillus anthracis are lethal in a murine model for pulmonary anthrax.
Bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. The capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. We show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to those of the parent strain. Mutants lacking one or more of the structural genes for the toxin proteins, i.e., protective antigen, lethal factor, and edema factor, disseminated from the lung to the spleen at rates similar to that of the virulent parental strain. The 50% lethal dose (LD50) and mean time to death (MTD) of the mutants did not differ significantly from those of the parent. The LD50s or MTDs were also unaffected relative to those of the parent strain when mice were inoculated intravenously with vegetative cells. Nonetheless, histopathological examination of tissues revealed subtle but distinct differences in infections by the parent compared to some toxin mutants, suggesting that the host response is affected by toxin proteins synthesized during infection.
Heninger
Sara
S
Department of Molecular Genetics and Microbiology, University of New Mexico Health Science Center, 1 University of New Mexico, Albuquerque, NM 87131, USA.
Drysdale
Melissa
M
Lovchik
Julie
J
Hutt
Julie
J
Lipscomb
Mary F
MF
Koehler
Theresa M
TM
Lyons
C Rick
CR
D000818:Animals; D000881:Anthrax / Q000382:microbiology* / Q000401:mortality* / Q000473:pathology; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics*; D001408:Bacillus anthracis / Q000235:genetics* / Q000472:pathogenicity*; D016667:Bacterial Capsules / Q000096:biosynthesis / Q000235:genetics; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005804:Genes, Lethal; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000382:microbiology* / Q000401:mortality* / Q000473:pathology; D013171:Spores, Bacterial / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D037521:Virulence Factors; C030325:anthrax toxin