Bacillus anthracis

About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.

The pathology of experimental anthrax in rabbits exposed by inhalation and subcutaneous inoculation.

Abstract: ○ Objective. Although rhesus monkeys are considered to be an appropriate model for inhalational anthrax in humans, an alternative for vaccine and therapeutic efficacy studies is desirable. This study characterized the pathology of lethal anthrax in rabbits challenged by subcutaneous inoculation and aerosol exposure. Materials and Methods.--New Zealand white rabbits were exposed by subcutaneous inoculation or aerosol to lethal doses of Bacillus anthracis spores. Results. The pathology of anthrax in rabbits exposed by either route was similar, with principal findings occurring in the spleen, lymph nodes, lungs, gastrointestinal tract, and adrenal glands. The cardinal changes were hemorrhage, edema, and necrosis, with bacilli and limited leukocytic infiltration. Features that depended on the route of exposure included mediastinitis in aerosol-exposed rabbits, a primary dermal lesion after subcutaneous inoculation, and differences in the pattern of lymph node involvement. Lesions observed in rabbits were comparable to those of inhalational anthrax in humans and rhesus monkeys. Noteworthy differences included the lack of leukocytic infiltration in brain and meningeal lesions, the relatively mild mediastinal lesions, and a lower incidence of anthrax-related pneumonia in rabbits compared with humans. These differences may be attributed to the greater susceptibility of rabbits to anthrax. Increased susceptibility is associated with both reduced leukocytic response to the bacilli and a more rapid progression to death, which further limits development of leukocytic infiltrates in response to the basic lesions of hemorrhage and necrosis. Primary pneumonic foci of inhalational anthrax, which may be influenced by preexisting pulmonary lesions in humans, were not observed in our rabbits, which were free of preexisting pulmonary disease. Conclusion. Anthrax in rabbits may provide a useful model for evaluating prophylaxis and therapy against inhalational anthrax in humans.

Genetic variability of Bacillus anthracis and related species.

Abstract: We evaluated the abilities of pulsed-field gel electrophoresis (PFGE) and sequences of intergenic spacer regions (ISRs) between two highly conserved genes, 16S-23S rDNA and gyrB-gyrA ISRs, to detect variation in strains of Bacillus anthracis as well as two closely related species, B cereus ATCC 14579 and B mycoides ATCC 6462 For each restriction enzyme, (NotI, SfiI, and SmaI), the PFGE banding patterns for three B anthracis strains (Ames, Vollum, and Sterne) were identical However, closely related species could be differentiated from B anthracis and from each other PCR amplification of the 16S-23S rDNA ISR yielded a 143- to 144-bp fragment, showing identical sequences for B anthracis strains, one nucleotide deletion between B cerus and B anthracis, and 13 nucleotide differences between B mycoides and B anthracis The gyrase ISR sequences (121 bp) in B anthracis strains were also identical, but those in B cereus and B mycoides differed from that in B anthracis by 1 and 2 nucleotides, respectively, and from each other by only 1 nucleotide Given the diverse geographic origins of these B anthracis strains, this species is very homogenous We conclude that methods such as PFGE and sequences of ISRs may be useful in separating B anthracis from closely related species, but more sensitive methods are needed for strain identification of B anthracis

Anthrax Spores Make an Essential Contribution to Vaccine Efficacy

Abstract: Anthrax is caused by Bacillus anthracis, a gram-positive spore-forming bacterium. Septicemia and toxemia rapidly lead to death in infected mammal hosts. Currently used acellular vaccines against anthrax consist of protective antigen (PA), one of the anthrax toxin components. However, in experimental animals such vaccines are less protective than live attenuated strains. Here we demonstrate that the addition of formaldehyde-inactivated spores (FIS) of B. anthracis to PA elicits total protection against challenge with virulent B. anthracis strains in mice and guinea pigs. The toxin-neutralizing activities of sera from mice immunized with PA alone or PA plus FIS were similar, suggesting that the protection conferred by PA plus FIS was not only a consequence of the humoral response to PA. A PA-deficient challenge strain was constructed, and its virulence was due solely to its multiplication. Immunization with FIS alone was sufficient to protect mice partially, and guinea pigs totally, against infection with this strain. This suggests that spore antigens contribute to protection. Guinea pigs and mice had very different susceptibilities to infection with the nontoxigenic strain, highlighting the importance of verifying the pertinence of animal models for evaluating anthrax vaccines.

Apoptosis and melanogenesis in human melanoma cells induced by anthrax lethal factor inactivation of mitogen-activated protein kinase kinase

Abstract: Lethal factor, the principal virulence factor of Bacillus anthracis, inhibits mitogen-activated protein kinase (MAPK) signaling by proteolytically cleaving MAPK kinases. Edema factor, another component of anthrax toxin, is an adenylate cyclase, which increases intracellular cAMP. Inhibition of MAPK signaling with either anthrax lethal toxin (LeTx) or small molecule MAPK kinase inhibitors triggers apoptosis in human melanoma cells. Normal melanocytes do not undergo apoptosis in response to MAPK inhibition but arrest in the G1 phase of the cell cycle. Importantly, in vivo treatment of human melanoma xenograft tumors in athymic nude mice with LeTx results in significant or complete tumor regression without apparent side effects, suggesting that inhibiting the MAPK signaling pathway may be a useful strategy for treating melanoma. Additionally, interrupting MAPK signaling with LeTx and elevating cAMP with anthrax edema toxin in both melanoma cells and melanocytes lead to dramatic melanin production, perhaps explaining the formation of blackened eschars in cutaneous anthrax.