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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
Les Baillie1
TL;DR: This paper will give a brief overview of the organism, its pathogenicity and the efforts being made to develop new vaccines.
Abstract: The disease anthrax is caused by a bacterium, Bacillus anthracis. Although primarily a disease of animals it can also infect man, sometimes with fatal consequences. Recent interest in the organism has centred on its ability to be employed as a biological weapon; the organism forms heat resistant spores which are easy to produce using commercially available technology and can infect humans via the aerosol route. At the time of the Gulf War it was reported that Iraq had produced and weaponized large quantities of anthrax spores (Zilinska 1997; www.anthrax.osd.mil/). As a consequence of this raised pro®le a considerable amount of effort has been focused on the development of new therapies that will meet the standards of the 21st century. Vaccination is the most cost-effective form of mass protection. While the ®rst anthrax animal vaccine was developed by Pasteur in 1881, human vaccines did not emerge until the middle of the 20th century. The vaccines currently available provide effective protection but suffer from problems of standardization, are relatively expensive to produce, require repeated dosing and have been associated with transient side-effects. This paper will give a brief overview of the organism, its pathogenicity and the efforts being made to develop new vaccines.

69 citations

Journal ArticleDOI
TL;DR: An overlooked population of anti-PA MAbs are described for the first time that function to increase the potency of LeTx against murine macrophage cell lines and support a possible mechanism of enhancement.
Abstract: We investigated the ability of using monoclonal antibodies (MAbs) against anthrax protective antigen (PA), an anthrax exotoxin component, to modulate exotoxin cytotoxic activity on target macrophage cell lines. Anthrax PA plays a critical role in the pathogenesis of Bacillus anthracis infection. PA is the cell-binding component of the two anthrax exotoxins: lethal toxin (LeTx) and edema toxin. Several MAbs that bind the PA component of LeTx are known to neutralize LeTx-mediated killing of target macrophages. Here we describe for the first time an overlooked population of anti-PA MAbs that, in contrast, function to increase the potency of LeTx against murine macrophage cell lines. The results support a possible mechanism of enhancement: binding of MAb to PA on the macrophage cell surface stabilizes the PA by interaction of MAb with macrophage Fcgamma receptors. This results in an increase in the amount of PA bound to the cell surface, which in turn leads to an enhancement in cell killing, most likely due to increased internalization of LF. Blocking of PA-receptor binding eliminates enhancement by MAb, demonstrating the importance of this step for the observed enhancement. The additional significance of these results is that, at least in mice, immunization with PA appears to elicit a poly-clonal response that has a significant prevalence of MAbs that enhance LeTx-mediated killing in macrophages.

68 citations

Journal ArticleDOI
TL;DR: It is suggested that W1 and W2 chimpanzee monoclonal antibodies may serve as PA entry inhibitors for use in the emergency prophylaxis against and treatment of anthrax.
Abstract: Four single-chain variable fragments (scFvs) against protective antigen (PA) and 2 scFvs against lethal factor (LF) of anthrax were isolated from a phage display library generated from immunized chimpanzees. Only 2 scFvs recognizing PA (W1 and W2) neutralized the cytotoxicity of lethal toxin in a macrophage lysis assay. Full-length immunoglobulin G (IgG) of W1 and W2 efficiently protected rats from anthrax toxin challenge. The epitope recognized by W1 and W2 was conformational and was formed by C-terminal amino acids 614-735 of PA. W1 and W2 each bound to PA with an equilibrium dissociation constant of 4 X 10 -11 mol/L to 5 X 10 -11 mol/L, which is an affinity that is 20-100-fold higher than that for the interaction of the receptor and PA. W1 and W2 inhibited the binding of PA to the receptor, suggesting that this was the mechanism of protection. These data suggest that W1 and W2 chimpanzee monoclonal antibodies may serve as PA entry inhibitors for use in the emergency prophylaxis against and treatment of anthrax.

68 citations

Journal ArticleDOI
TL;DR: This study indicates that B. anthracis virulence is associated with the clonality and virulence of plasmids pXO1 and pX o2, and developed a model predicting virulence.
Abstract: Bacillus anthracis is a bacterial pathogen of great importance, both historically and in the present. This study presents data collected from several investigations and indicates that B. anthracis virulence is associated with the clonality and virulence of plasmids pXO1 and pXO2. Guinea pigs vaccinated with Anthrax Vaccine Adsorbed were challenged with 20 B. anthracis isolates representative of worldwide genetic diversity. These same isolates were characterized with respect to plasmid copy number by using a novel method of quantitative PCR developed for rapid and efficient detection of B. anthracis from environmental samples. We found that the copy numbers for both pXO1 and pXO2 differed from those in previously published reports. By combining the data on survival, plasmid copy numbers, and clonality, we developed a model predicting virulence. This model was validated by using a randomly chosen set of 12 additional B. anthracis isolates. Results from this study will be helpful in future efforts to elucidate the basis for variation in the virulence of this important pathogen.

68 citations

Journal ArticleDOI
TL;DR: The observation of large differences due to less common variables indicates the complex nature of the force balance in optical chromatography, which may in the future be used to separate and characterize microbiological samples.
Abstract: A significant difference between two closely related Bacillus spores has been discovered using optical chromatography. This difference can be harnessed for the separation of microscopic particles using opposing laser and fluid flow forces. Particles of different size, composition, and shape experience different optical and fluid forces and come to rest at unique equilibrium positions where the two forces balance. Separations in excess of 600 μm have been observed between Bacillus anthracis Sterne strain and its genetic relative, Bacillus thuringiensis. These findings open new possibilities for detection and characterization of the biological warfare agent, B. anthracis, the causative agent of anthrax, the deadly mammalian disease. The large optical separation between these species is surprising given their close genetic relationship but may be explained by differences in their shape and exosporium morphology, which may result in differences in fluid drag force. The observation of large differences due to ...

68 citations


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