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: A number of approaches have been taken to identify LF inhibitors, from generating conventional metal chelating substrate analogs to random screening of diverse compound libraries, which have produced several different classes of specific nanomolar range inhibitors.
Abstract: Anthrax is caused by infection with Bacillus anthracis, a spore forming, rod-shaped, encapsulated gram positive bacteria. The disease manifests itself in distinct ways depending on the route of entry of infective bacterial spores: cutaneous, inhalational, and gastrointestinal. Though rare in humans, inhalational anthrax has become a major concern due to the capacity for spores to be weaponized. The limited success of antibiotic therapy has motivated investigation of complementary therapeutic strategies that target the bacteria's secreted toxin. The zinc-dependent metalloproteinase lethal factor (LF) is a critical component of anthrax toxin and an important potential target for small molecule drugs. In the past few years, a number of approaches have been taken to identify LF inhibitors, from generating conventional metal chelating substrate analogs to random screening of diverse compound libraries. These efforts have produced several different classes of specific nanomolar range inhibitors. Some compounds have fared well in animal models for anthrax toxemia and infection, and these inhibitors and their derivatives may form the basis for future therapies to treat the disease in humans.
42 citations
TL;DR: An automated DNA electrophoresis apparatus which provides a cheaper alternative compared to capillary electrophoreis approaches was applied for genotyping of B. anthracis and Y. pesti s and is a candidate for on-site MLVA genotypes of biothreat agents as well as other bacterial pathogens.
Abstract: Anthrax and plague are diseases caused by Bacillus anthracis and Yersinia pestis respectively. These bacteria are etiological agents for worldwide zoonotic diseases and are considered among the most feared potential bioterror agents. Strain differentiation is difficult for these microorganisms because of their high intraspecies genome homogeneity. Moreover, fast strain identification and comparison with known genotypes may be crucial for naturally occurring outbreaks versus bioterrorist events discrimination. Thirty-nine B. anthracis and ten Y. pestis strains, representative of the species genetic diversity, were genotyped by Agilent 2100 Bioanalyzer using previously described Multiple Locus VNTR Analysis assays (MLVA). Results were compared to previous data obtained by standard genotyping system (capillary electrophoresis on automatic sequencer) and, when necessary, direct amplicon sequencing. A reference comparison table containing actual fragment sizes, sequencer sizes and Agilent sizes was produced. In this report an automated DNA electrophoresis apparatus which provides a cheaper alternative compared to capillary electrophoresis approaches was applied for genotyping of B. anthracis and Y. pesti s. This equipment, uses pre-cast gels and provides easy transportation, low maintenance and overall general logistic requirements and costs, is easy to set up and provides rapid analysis. This platform is a candidate for on-site MLVA genotyping of biothreat agents as well as other bacterial pathogens. It is an alternative to the more expensive and demanding capillary electrophoresis methods, and to the less expensive but more time-consuming classical gel electrophoresis approach.
42 citations
TL;DR: Results showed that the environmental variables can adequately predict the ecological niche of B. anthracis (AUC for test data=0.717, p<0.001), which implies that the model tested may be used by animal health authorities in devising better control strategies for anthrax.
42 citations
TL;DR: The addition of soil variables to the previously developed ecological niche model did not appreciably alter the limits of the predicted geographic or ecological distribution of B. anthracis in Kazakhstan and supports careful consideration of the taxonomic resolution of data used to create ecological niche models.
Abstract: Background Bacillus anthracis , the causative agent of anthrax, is a globally distributed zoonotic pathogen that continues to be a veterinary and human health problem in Central Asia. We used a database of anthrax outbreak locations in Kazakhstan and a subset of genotyped isolates to model the geographic distribution and ecological associations of B. anthracis in Kazakhstan. The aims of the study were to test the influence of soil variables on a previous ecological niche based prediction of B. anthracis in Kazakhstan and to determine if a single sub-lineage of B. anthracis occupies a unique ecological niche. Results The addition of soil variables to the previously developed ecological niche model did not appreciably alter the limits of the predicted geographic or ecological distribution of B. anthracis in Kazakhstan. The A1.a experiment predicted the sub-lineage to be present over a larger geographic area than did the outbreak based experiment containing multiple lineages. Within the geographic area predicted to be suitable for B. anthracis by all ten best subset models, the A1.a sub-lineage was associated with a wider range of ecological tolerances than the outbreak-soil experiment. Analysis of rule types showed that logit rules predominate in the outbreak-soil experiment and range rules in the A1.a sub-lineage experiment. Random sub-setting of locality points suggests that models of B. anthracis distribution may be sensitive to sample size. Conclusions Our analysis supports careful consideration of the taxonomic resolution of data used to create ecological niche models. Further investigations into the environmental affinities of individual lineages and sub-lineages of B. anthracis will be useful in understanding the ecology of the disease at large and small scales. With model based predictions serving as approximations of disease risk, these efforts will improve the efficacy of public health interventions for anthrax prevention and control.
42 citations
TL;DR: Haines et al. as discussed by the authors used the time-to-death of the intravenously challenged Fischer 344 rat as the response variable to define a potency unit of the crude anthrax toxins.
Abstract: Haines, Bertram W. (U.S. Army Biological Laboratories, Frederick, Md.), Frederick Klein, and Ralph E. Lincoln. Quantitative assay for crude anthrax toxins. J. Bacteriol. 89:74–83. 1965.—The whole crude toxins of Bacillus anthracis, although apparently responsible for the death of animals with anthrax, had never been quantitated. A total of 14 lots of the toxic culture filtrate of B. anthracis were pooled into one large lot of crude anthrax toxins. An extensive assay of this reference material was conducted in four laboratories by use of the time-to-death of the intravenously challenged Fischer 344 rat as the response variable. Doses of the material were varied factorially by concentration, dilution, and volume. The data from this study were used to define a potency unit of the crude anthrax toxins. Procedures were developed and illustrated for the assay of unknown lots of the toxins by comparing the rat time-to-death response to the unknown with either (i) the responses reported in this study, or (ii) directly with the rat responses to a new sample of the reference toxins. The possibilities and limitations of this standardization and of the statistical procedure through which it was developed are discussed.
42 citations