Topic
Bacillus anthracis
About: Bacillus anthracis is a research topic. Over the lifetime, 3994 publications have been published within this topic receiving 128122 citations.
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TL;DR: It is reported that caspase‐1‐mediated IL‐1β expression in response to BA spores is required for anti‐BA host defenses, and different components of the same bacterium each induce IL-1β by distinct signaling pathways.
Abstract: Previous reports suggested that lethal toxin (LT)-induced caspase-1 activity and/or IL-1β accounted for Bacillus anthracis (BA) infection lethality. In contrast, we now report that caspase-1-mediated IL-1β expression in response to BA spores is required for anti-BA host defenses. Caspase-1–/– and IL-1β–/– mice are more susceptible than wild-type (WT) mice to lethal BA infection, are less able to kill BA both in vivo and in vitro, and addition of rIL-1β to macrophages from these mice restored killing in vitro. Non-germinating BA spores induced caspase-1 activity, IL-1β and nitric oxide, by which BA are killed in WT but not in caspase-1–/– mice, suggesting that the spore itself stimulated inflammatory responses. While spores induced IL-1β in LT-susceptible and -resistant macrophages, LT induced IL-1β only in LT-susceptible macrophages. Cooperation between MyD88-dependent and -independent signaling pathways was required for spore-induced, but not LT-induced, IL-1β. While both spores and LT induced caspase-1 activity and IL-1β, LT did not induce IL-1β mRNA, and spores did not induce cell death. Thus different components of the same bacterium each induce IL-1β by distinct signaling pathways. Whereas the spore-induced IL-1β limits BA infection, LT-induced IL-1β enables BA to escape host defenses.
Supporting Information for this article is available at www.wiley-vch.de/contents/jc_2040/2008/38141_s.pdf
43 citations
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TL;DR: It is reported that infection of a murine macrophage cell line with Bacillus anthracis results in the production of tumor necrosis factor alpha and interleukin-12 (IL-12) and no evidence of inhibition of cytokine responses in macrophages infected with B. Anthracis spores is found.
Abstract: Herein we report that infection of a murine macrophage cell line with Bacillus anthracis results in the production of tumor necrosis factor alpha and interleukin-12 (IL-12). When infected with B. anthracis spores in combination with lipopolysaccharide, macrophages release increased amounts of IL-12. We found no evidence of inhibition of cytokine responses in macrophages infected with B. anthracis spores.
43 citations
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TL;DR: This work investigates the contribution of the individual toxins to BBB disruption using isogenic toxin mutants deficient in lethal factor, ΔLF, and edema factor, and observed that toxin expression reduced bacterial intracellular survival by inducing the bulk degradative autophagy pathway in host cells.
Abstract: Bacillus anthracis is a Gram-positive spore-forming bacterium that causes anthrax disease in humans and animals. Systemic infection is characterized by septicemia, toxemia, and meningitis, the main neurological complication associated with high mortality. We have shown previously that B. anthracis Sterne is capable of blood-brain barrier (BBB) penetration, establishing the classic signs of meningitis, and that infection is dependent on the expression of both major anthrax toxins, lethal toxin (LT) and edema toxin (ET). Here we further investigate the contribution of the individual toxins to BBB disruption using isogenic toxin mutants deficient in lethal factor, ΔLF, and edema factor, ΔEF. Acute infection with B. anthracis Sterne and the ΔLF mutant resulted in disruption of human brain microvascular endothelial cell (hBMEC) monolayer integrity and tight junction protein zona occludens-1, while the result for cells infected with the ΔEF mutant was similar to that for the noninfected control. A significant decrease in bacterial invasion of BBB endothelium in vitro was observed during infection with the ΔLF strain, suggesting a prominent role for LT in promoting BBB interaction. Further, treatment of hBMECs with purified LT or chemicals that mimic LT action on host signaling pathways rescued the hypoinvasive phenotype of the ΔLF mutant and resulted in increased bacterial uptake. We also observed that toxin expression reduced bacterial intracellular survival by inducing the bulk degradative autophagy pathway in host cells. Finally, in a murine model of anthrax meningitis, mice infected with the ΔLF mutant exhibited no mortality, brain bacterial load, or evidence of meningitis compared to mice infected with the parental or ΔEF strains.
43 citations
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TL;DR: A fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method that produced fluorescent patterns that acted as a visual alarm against anthrax.
43 citations
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TL;DR: The potential use of electrospray for encapsulating protein antigens in polymeric MPs is demonstrated and BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain.
Abstract: Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress. rPA and the adjuvant resiquimod are encapsulated either in separate or the same acetalated dextran MPs. Using a murine model, the electrospray formulations lead to higher IgG2a subtype titers as well as comparable total IgG antibody titers and toxin neutralization relative to the FDA-approved vaccine (BioThrax). BioThrax provides no protection against a lethal inhalational challenge of the highly virulent Ames Bacillus anthracis anthrax strain, whereas 50% of the mice vaccinated with separately encapsulated electrospray MPs survive. Overall, this study demonstrates the potential use of electrospray for encapsulating protein antigens in polymeric MPs.
43 citations