-
Expert Review of Vaccines Feb 2008We have reviewed the information about epitopes of immunological interest from Clostridium botulinum and Bacillus anthracis, by mining the Immune Epitope Database and... (Review)
Review
We have reviewed the information about epitopes of immunological interest from Clostridium botulinum and Bacillus anthracis, by mining the Immune Epitope Database and Analysis Resource. For both pathogens, the vast majority of epitopes reported to date are derived from a single protein: the protective antigen of B. anthracis and the neurotoxin type A of C. botulinum. A detailed analysis of the data was performed to characterize the function, localization and conservancy of epitopes identified as neutralizing and/or protective. In order to broaden the scope of this analysis, we have also included data describing immune responses against defined fragments (over 50 amino acids long) of the relevant antigens. The scarce information on T-cell determinants and on epitopes from other antigens besides the toxins, highlights a gap in our knowledge and identifies areas for future research. Despite this, several distinct structures at the epitope and fragment level are described herein, which could be potential additions to future vaccines or targets of novel immunotherapeutics and diagnostic reagents.
Topics: Antigens, Bacterial; Bacillus anthracis; Clostridium botulinum; Epitopes; Neutralization Tests
PubMed: 18251694
DOI: 10.1586/14760584.7.1.55 -
MicrobiologyOpen Oct 2022Spores are an infectious form of the zoonotic bacterial pathogen, Bacillus anthracis. The outermost spore layer is the exosporium, comprised of a basal layer and an...
Spores are an infectious form of the zoonotic bacterial pathogen, Bacillus anthracis. The outermost spore layer is the exosporium, comprised of a basal layer and an external glycoprotein nap layer. The major structural proteins of the inner basal layer are CotY (at the mother cell central pole or bottlecap) and ExsY around the rest of the spore. The basis for the cap or noncap specificity of the CotY and ExsY proteins is currently unknown. We investigated the role of sequence differences between these proteins in localization during exosporium assembly. We found that sequence differences were less important than the timing of expression of the respective genes in the positioning of these inner basal layer structural proteins. Fusion constructs with the fluorescent protein fused at the N-terminus resulted in poor incorporation whereas fusions at the carboxy terminus of CotY or ExsY resulted in good incorporation. However, complementation studies revealed that fusion constructs, although accurate indicators of protein localization, were not fully functional. A model is presented that explains the localization patterns observed. Bacterial two-hybrid studies in Escherichia coli hosts were used to examine protein-protein interactions with full-length and truncated proteins. The N-terminus amino acid sequences of ExsY and CotY appear to be recognized by spore proteins located in the spore interspace, consistent with interactions seen with ExsY and CotY with the interspace proteins CotE and CotO, known to be involved with exosporium attachment.
Topics: Bacillus anthracis; Spores, Bacterial; Bacterial Proteins; Cell Wall; Spores
PubMed: 36314748
DOI: 10.1002/mbo3.1327 -
Molecular Microbiology Oct 2016The dramatic, rapid growth of Bacillus anthracis that occurs during systemic anthrax implies a crucial requirement for the efficient acquisition of iron. While recent... (Review)
Review
The dramatic, rapid growth of Bacillus anthracis that occurs during systemic anthrax implies a crucial requirement for the efficient acquisition of iron. While recent advances in our understanding of B. anthracis iron acquisition systems indicate the use of strategies similar to other pathogens, this review focuses on unique features of the major siderophore system, petrobactin. Ways that petrobactin differs from other siderophores include: A. unique ferric iron binding moieties that allow petrobactin to evade host immune proteins; B. a biosynthetic operon that encodes enzymes from both major siderophore biosynthesis classes; C. redundancy in membrane transport systems for acquisition of Fe-petrobactin holo-complexes; and, D. regulation that appears to be controlled predominately by sensing the host-like environmental signals of temperature, CO levels and oxidative stress, as opposed to canonical sensing of intracellular iron levels. We argue that these differences contribute in meaningful ways to B. anthracis pathogenesis. This review will also outline current major gaps in our understanding of the petrobactin iron acquisition system, some projected means for exploiting current knowledge, and potential future research directions.
Topics: Bacillus anthracis; Bacterial Proteins; Benzamides; Iron; Operon; Siderophores
PubMed: 27425635
DOI: 10.1111/mmi.13465 -
Annals of Agricultural and... 2012Articles concerning new aspects of B. anthracis mechanisms of infection were reviewed. It was found, that the hair follicle plays an important role in the spore... (Review)
Review
Articles concerning new aspects of B. anthracis mechanisms of infection were reviewed. It was found, that the hair follicle plays an important role in the spore germination process. The hair follicle represent an important portal of entry in the course of the cutaneous form of disease infections. After mouse exposition to aerosol of spores prepared from B. anthracis strains, an increase in the level of TNF-α cytokines was observed. The TNF-α cytokines were produced after intrusion into the host by the microorganism. This process may play a significant role in the induced migration of infected cells APCs (Antigen Presenting Cells) via chemotactic signals to the lymph nodes. It was explained that IgG, which binds to the spore surface, activates the adaptive immune system response. As a result, the release C3b opsonin from the spore surface, and mediating of C3 protein fragments of B. anthracis spores phagocytosis by human macrophages, was observed. The genes coding germination spores protein in mutant strains of B. anthracis MIGD was a crucial discovery. According to this, it could be assumed that the activity of B. anthracis spores germination process is dependent upon the sleB, cwlJ1 and cwlJ2 genes, which code the GSLEs lithic enzymes. It was also discovered that the specific antibody for PA20, which binds to the PA20 antigenic determinant, are able to block further PA83 proteolytic fission on the surface of cells. This process neutralized PA functions and weakened the activity of free PA20, which is produced during the PA83 enzyme fission process. Interaction between PA63 monomer and LF may be helpful in the PA63 oligomerization and grouping process, and the creation of LF/PA63 complexes may be a part of an alternative process of assembling the anthrax toxin on the surface of cells. It was found that actin-dependent endocytosis plays an important role in the PA heptamerisation process and leads to blocking the toxin activity. Chaperones, a protein derived from host cells, may be helpful in ATP and cytosolic factors translocation, and in this way increase the translocation of diphteria toxin A domein (DTA) and substrate of fusion protein LF(N)-DTA.
Topics: Animals; Anthrax; Antigens, Bacterial; Bacillus anthracis; Bacterial Toxins; Humans; Spores, Bacterial
PubMed: 23311776
DOI: No ID Found -
PLoS Neglected Tropical Diseases 2012The recent development of genetic markers for Bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax...
The recent development of genetic markers for Bacillus anthracis has made it possible to monitor the spread and distribution of this pathogen during and between anthrax outbreaks. In Namibia, anthrax outbreaks occur annually in the Etosha National Park (ENP) and on private game and livestock farms. We genotyped 384 B. anthracis isolates collected between 1983-2010 to identify the possible epidemiological correlations of anthrax outbreaks within and outside the ENP and to analyze genetic relationships between isolates from domestic and wild animals. The isolates came from 20 animal species and from the environment and were genotyped using a 31-marker multi-locus-VNTR-analysis (MLVA) and, in part, by twelve single nucleotide polymorphism (SNP) markers and four single nucleotide repeat (SNR) markers. A total of 37 genotypes (GT) were identified by MLVA, belonging to four SNP-groups. All GTs belonged to the A-branch in the cluster- and SNP-analyses. Thirteen GTs were found only outside the ENP, 18 only within the ENP and 6 both inside and outside. Genetic distances between isolates increased with increasing time between isolations. However, genetic distance between isolates at the beginning and end of the study period was relatively small, indicating that while the majority of GTs were only found sporadically, three genetically close GTs, accounting for more than four fifths of all the ENP isolates, appeared dominant throughout the study period. Genetic distances among isolates were significantly greater for isolates from different host species, but this effect was small, suggesting that while species-specific ecological factors may affect exposure processes, transmission cycles in different host species are still highly interrelated. The MLVA data were further used to establish a model of the probable evolution of GTs within the endemic region of the ENP. SNR-analysis was helpful in correlating an isolate with its source but did not elucidate epidemiological relationships.
Topics: Animals; Anthrax; Bacillus anthracis; Cluster Analysis; Disease Outbreaks; Environmental Microbiology; Evolution, Molecular; Genetic Variation; Genotype; Minisatellite Repeats; Molecular Epidemiology; Molecular Typing; Namibia; Polymorphism, Single Nucleotide
PubMed: 22413024
DOI: 10.1371/journal.pntd.0001534 -
PLoS Neglected Tropical Diseases 2015Zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries....
Zoonoses, diseases affecting both humans and animals, can exert tremendous pressures on human and veterinary health systems, particularly in resource limited countries. Anthrax is one such zoonosis of concern and is a disease requiring greater public health attention in Nigeria. Here we describe the genetic diversity of Bacillus anthracis in Nigeria and compare it to Chad, Cameroon and a broader global dataset based on the multiple locus variable number tandem repeat (MLVA-25) genetic typing system. Nigerian B. anthracis isolates had identical MLVA genotypes and could only be resolved by measuring highly mutable single nucleotide repeats (SNRs). The Nigerian MLVA genotype was identical or highly genetically similar to those in the neighboring countries, confirming the strains belong to this unique West African lineage. Interestingly, sequence data from a Nigerian isolate shares the anthrose deficient genotypes previously described for strains in this region, which may be associated with vaccine evasion. Strains in this study were isolated over six decades, indicating a high level of temporal strain stability regionally. Ecological niche models were used to predict the geographic distribution of the pathogen for all three countries. We describe a west-east habitat corridor through northern Nigeria extending into Chad and Cameroon. Ecological niche models and genetic results show B. anthracis to be ecologically established in Nigeria. These findings expand our understanding of the global B. anthracis population structure and can guide regional anthrax surveillance and control planning.
Topics: Animals; Anthrax; Bacillus anthracis; Bacterial Typing Techniques; Cameroon; Cattle; Cattle Diseases; Chad; Genetic Variation; Genotype; Humans; Minisatellite Repeats; Molecular Sequence Data; Nigeria; Phylogeny
PubMed: 26291625
DOI: 10.1371/journal.pntd.0003931 -
Research in Microbiology Nov 2010Fifteen years ago, AtxA was isolated as a toxin gene activator and five years later it was shown to be a Bacillus anthracis master regulator. AtxA controls the... (Review)
Review
Fifteen years ago, AtxA was isolated as a toxin gene activator and five years later it was shown to be a Bacillus anthracis master regulator. AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. The mechanism by which AtxA exerts its control is unknown; it is indirect on some genes but may be direct on others. The expression of many AtxA-controlled genes is induced by the presence of bicarbonate/CO(2). AtxA links the metabolic state and virulence gene expression.
Topics: Animals; Anthrax; Bacillus anthracis; Bacterial Proteins; Gene Expression Regulation, Bacterial; Genes, Regulator; Humans; Trans-Activators; Virulence
PubMed: 20863885
DOI: 10.1016/j.resmic.2010.09.006 -
Journal of Bacteriology Jul 2020, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is required for the retention of surface layer (S-layer) and...
, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is required for the retention of surface layer (S-layer) and S-layer homology (SLH) domain proteins. Genetic disruption of the SCWP biosynthetic pathway impairs growth and cell division. SCWP is comprised of trisaccharide repeats composed of one ManNAc and two GlcNAc residues with O-3-α-Gal and O-4-β-Gal substitutions. UDP-Gal, synthesized by GalE1, is the substrate of galactosyltransferases that modify the SCWP repeat. Here, we show that the gene, which encodes a predicted glycosyltransferase with a GT-A fold, is required for O-4-β-Gal modification of trisaccharide repeats. We identify a DXD motif critical for GtsE activity. Three distinct genes, , , and , are required for O-3-α-Gal modification of trisaccharide repeats. Based on the similarity with other three-component glycosyltransferase systems, we propose that GtsA transfers Gal from cytosolic UDP-Gal to undecaprenyl phosphate (C-P), GtsB flips the C-P-Gal intermediate to the side of the membrane, and GtsC transfers Gal onto trisaccharide repeats. The deletion of does not affect growth , suggesting that galactosyl modifications are dispensable for the function of SCWP. The deletion of , , or leads to a loss of viability, yet and can be deleted in strains lacking or We propose that the loss of viability is caused by the accumulation of undecaprenol-bound precursors and present an updated model for SCWP assembly in to account for the galactosylation of repeat units. Peptidoglycan is a conserved extracellular macromolecule that protects bacterial cells from turgor pressure. Peptidoglycan of Gram-positive bacteria serves as a scaffold for the attachment of polymers that provide defined bacterial interactions with their environment. One such polymer, SCWP, is pyruvylated at its distal end to serve as a receptor for secreted proteins bearing the S-layer homology domain. Repeat units of SCWP carry three galactoses in Glycosylation is a recurring theme in nature and often represents a means to mask or alter conserved molecular signatures from intruders such as bacteriophages. Several glycosyltransferase families have been described based on bioinformatics prediction, but few have been studied. Here, we describe the glycosyltransferases that mediate the galactosylation of SCWP.
Topics: Anthrax; Bacillus anthracis; Bacterial Proteins; Cell Wall; Galactose; Gene Deletion; Gene Expression Regulation, Bacterial; Glycosylation; Humans; Polysaccharides, Bacterial
PubMed: 32457049
DOI: 10.1128/JB.00191-20 -
Research in Microbiology 2023Bacillus anthracis is a spore-forming bacterium that produces two major virulence factors, a tripartite toxin with two enzymatic toxic activities and a pseudo-proteic...
Bacillus anthracis is a spore-forming bacterium that produces two major virulence factors, a tripartite toxin with two enzymatic toxic activities and a pseudo-proteic capsule. One of the main described functions of the poly-gamma-d-glutamate capsule is to enable B. anthracis bacilli to escape phagocytosis. Thus, kinetics of expression of the capsule filaments at the surface of the emerging bacillus during germination is an important step for the protection of the nascent bacilli. In this study, through immunofluorescence and electron microscopic approaches, we show the emergence of the capsule through a significant surface of the exosporium in the vast majority of the germinating spores, with co-detection of BclA and capsular material. This suggests that, due to an early capsule expression, the extracellular life of B. anthracis might occur earlier than previously thought, once germination is triggered. This raises the prospect that an anti-capsular vaccine may play a protective role at the initial stage of infection by opsonisation of the nascent encapsulated bacilli before their emergence from the exosporium.
Topics: Bacillus anthracis; Spores, Bacterial
PubMed: 37003307
DOI: 10.1016/j.resmic.2023.104054 -
Journal of Applied Microbiology Aug 1999The word 'problem' is seen with some frequency in relation to clear differentiation between Bacillus anthracis and B. cereus. In fact, although the close relationship of... (Review)
Review
The word 'problem' is seen with some frequency in relation to clear differentiation between Bacillus anthracis and B. cereus. In fact, although the close relationship of these two species is undisputed, it is only in the case of a few borderline isolates, rarely encountered in practice, that any sort of identification problem exists. Until recently this was only important to the taxonomist who found it unsatisfactory not to be able to identify definitively such isolates. To most others, if the isolate was unable to produce anthrax in a laboratory animal, it was discarded as irrelevant without being named, or it was called B. cereus or given a name such as B. anthracis similis, or even a totally unrelated name. More recently, in view of the new light in which B. anthracis is increasingly seen, resulting from its putative association with bioaggression, clear identification has become a more critical issue. This paper reviews the current state of the art and suggests the way forward for the future.
Topics: Animals; Anthrax; Bacillus; Bacillus anthracis; Bacterial Typing Techniques; Genetic Variation; Genome, Bacterial; Humans
PubMed: 10475956
DOI: 10.1046/j.1365-2672.1999.00876.x