Pathogenesis and genetic control of resistance to the Sterne strain of Bacillus anthracis.
The pathogenesis of lethal infection by the nonecapsulated, toxigenic Sterne strain of Bacillus anthracis and the genetic basis of resistance were characterized in mice. Lethal doses of Sterne spores produced disease in susceptible mice similar to that caused by toxigenic and encapsulated B. anthracis. At the inoculation site, the mice developed an edematous exudate with large concentrations of bacilli and toxin. In the susceptible A/J strain, lethal infection was accompanied by systemic invasion and serum anthrax toxin levels increased in parallel with systemic bacterial concentrations and with the mortality rate. Host resistance to Sterne infection was associated with the ability to synthesize the complement component 5 (C5). All Sterne-resistant mouse strains had a functional gene (Hc) encoding C5, whereas susceptible mice were deficient in C5. A/J mice could be passively protected from lethal challenge by C5-positive serum but not by serum from C5-negative congenic mice. Also resistance was linked to production of C5 in individual backcross (97%) and F2 (98%) mice. The distribution pattern for recombinant inbred mice was consistent with a major role in host resistance of Hc or a closely linked locus, although other genes probably contribute. This mouse model will be useful in characterizing the pathogenesis of anthrax and testing the safety and efficacy of new anthrax vaccines.
D000818:Animals; D000881:Anthrax / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D000942:Antigens, Bacterial / Q000032:analysis; D001408:Bacillus anthracis / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D001427:Bacterial Toxins / Q000096:biosynthesis / Q000276:immunology; D015153:Blotting, Western; D003182:Complement C5 / Q000096:biosynthesis / Q000235:genetics; D004198:Disease Susceptibility; D004487:Edema; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate; D051379:Mice; D008815:Mice, Inbred Strains; D013171:Spores, Bacterial
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D003182:Complement C5; C030325:anthrax toxin