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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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Journal ArticleDOI
08 Mar 2002-Science
TL;DR: The anthrax outbreak in the United States in fall 2001 resulted from the intentional dissemination of Bacillus anthracis spores and public health authorities recommended that some groups of individuals undergo a 60-day regimen of antimicrobial prophylaxis.
Abstract: The anthrax outbreak in the United States in fall 2001 resulted from the intentional dissemination of Bacillus anthracis spores ([1][1]). In response to the outbreak, public health authorities recommended that some groups of individuals undergo a 60-day regimen of antimicrobial prophylaxis (AP) ([2

68 citations

Journal ArticleDOI
TL;DR: Using a simple, two-step protocol, double mutant strains of B. anthracis producing only one toxin component have been constructed and characterization of the mutant strains indicated that they produced the expected single toxin protein.
Abstract: SUMMARY: The two protein exotoxins secreted by Bacillus anthvacis are composed of three distinct components: protective antigen (PA), lethal factor (LF), and (o)edema factor (EF). We have developed a genetic strategy that permits us selectively to inactivate each of the genes coding for PA, EF or LF. This strategy involved the deletion of a portion of the structural gene and the insertion of an antibiotic resistance cassette. With this technique, double mutant strains of B. anthracis producing only one toxin component have been constructed. Characterization of the mutant strains indicated that they produced the expected single toxin protein. Using a simple, two-step protocol, we have purified PA, LF and EF to homogeneity from culture supernatants. These three mutant strains are potentially powerful tools for studying the individual effect of each toxin component in vitro and in vivo.

67 citations

Journal ArticleDOI
05 Nov 2009-Vaccine
TL;DR: This review summarizes the various approaches used to develop improved vaccines, which have included the use of PA with newer adjuvants and delivery systems, including bacterial and viral vectors and DNA vaccines.

67 citations

Journal ArticleDOI
TL;DR: A series of new β-cyclodextrin derivatives with alkyl spacers of various lengths are evaluated to identify a new class of drugs for anthrax treatment that block the pathway for toxin translocation into the cytosol, the PA channel.
Abstract: Recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of β-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (PA) subunit of the toxin. In the present study, we evaluate a series of new β-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. Newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of β-cyclodextrin with alkyl spacers of various lengths were tested for the ability to inhibit cytotoxicity of lethal toxin in cells as well as to block ion conductance through PA channels reconstituted in planar bilayer lipid membranes. Most of the tested derivatives were protective against anthrax lethal toxin action at low or submicromolar concentrations. They also blocked ion conductance through PA channels at concentrations as low as 0.1 nM. The activities of the derivatives in both cell protection and channel blocking were found to depend on the length and chemical nature of the substituent groups. One of the compounds was also shown to block the edema toxin activity. It is hoped that these results will help to identify a new class of drugs for anthrax treatment, i.e., drugs that block the pathway for toxin translocation into the cytosol, the PA channel.

67 citations

Journal ArticleDOI
TL;DR: The strategies described provide a foundation to discover human antibodies specific for native spores of B. anthracis that can be developed as diagnostic and therapeutic reagents and developed by using fluorescently labeled antibody-phage.
Abstract: A naive, human single-chain Fv (scFv) phage-display library was used in bio-panning against live, native spores of Bacillus subtilis IFO 3336 suspended in solution. A direct in vitro panning and enzyme-linked immunosorbent assay-based selection afforded a panel of nine scFv-phage clones of which two, 5B and 7E, were chosen for further study. These two clones differed in their relative specificity and affinity for spores of B. subtilis IFO 3336 vs. a panel of spores from 11 other Bacillus species/strains. A variety of enzyme-linked immunosorbent assay protocols indicated these scFv-phage clones recognized different spore epitopes. Notably, some spore epitopes markedly changed between the free and microtiter-plate immobilized state as revealed by antibody-phage binding. An additional library selection procedure also was examined by constructing a Fab chain-shuffled sublibrary from the nine positive clones and by using a subtractive panning strategy to remove crossreactivity with B. licheniformis 5A24. The Fab-phage clone 52 was improved compared with 5B and was comparable to 7E in binding B. subtilis IFO 3336 vs. B. licheniformis 5A24, yet showed a distinctive crossreactivity pattern with other spores. We also developed a method to directly detect individual spores by using fluorescently labeled antibody-phage. Finally, a variety of “powders” that might be used in deploying spores of B. anthracis were examined for antibody-phage binding. The strategies described provide a foundation to discover human antibodies specific for native spores of B. anthracis that can be developed as diagnostic and therapeutic reagents.

67 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20241
202381
2022169
202181
2020116
2019106