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Annual Review of Microbiology Sep 2017Bacillus anthracis, the anthrax agent, is a member of the Bacillus cereus sensu lato group, which includes invasive pathogens of mammals or insects as well as... (Review)
Review
Bacillus anthracis, the anthrax agent, is a member of the Bacillus cereus sensu lato group, which includes invasive pathogens of mammals or insects as well as nonpathogenic environmental strains. The genes for anthrax pathogenesis are located on two large virulence plasmids. Similar virulence plasmids have been acquired by other B. cereus strains and enable the pathogenesis of anthrax-like diseases. Among the virulence factors of B. anthracis is the S-layer-associated protein BslA, which endows bacilli with invasive attributes for mammalian hosts. BslA surface display and function are dependent on the bacterial S-layer, whose constituents assemble by binding to the secondary cell wall polysaccharide (SCWP) via S-layer homology (SLH) domains. B. anthracis and other pathogenic B. cereus isolates harbor genes for the secretion of S-layer proteins, for S-layer assembly, and for synthesis of the SCWP. We review here recent insights into the assembly and function of the S-layer and the SCWP.
Topics: Bacillus anthracis; Membrane Glycoproteins; Protein Multimerization
PubMed: 28622090
DOI: 10.1146/annurev-micro-090816-093512 -
Infection, Genetics and Evolution :... Oct 2018Bacillus anthracis, the etiological agent of anthrax, procures its particular virulence by a capsule and two AB type toxins: the lethal factor LF and the edema factor... (Review)
Review
Bacillus anthracis, the etiological agent of anthrax, procures its particular virulence by a capsule and two AB type toxins: the lethal factor LF and the edema factor EF. These toxins primarily disable immune cells. Both toxins are translocated to the host cell by the adhesin-internalin subunit called protective antigen PA. PA enables LF to reach intra-luminal vesicles, where it remains active for long periods. Subsequently, LF translocates to non-infected cells, leading to inefficient late therapy of anthrax. B. anthracis undergoes slow evolution because it alternates between vegetative and long spore phases. Full genome sequence analysis of a large number of worldwide strains resulted in a robust evolutionary reconstruction of this bacterium, showing that B. anthracis is split in three main clades: A, B and C. Clade A efficiently disseminated worldwide underpinned by human activities including heavy intercontinental trade of goat and sheep hair. Subclade A.Br.WNA, which is widespread in the Northern American continent, is estimated to have split from clade A reaching the Northern American continent in the late Pleistocene epoch via the former Bering Land Bridge and further spread from Northwest southwards. An alternative hypothesis is that subclade A.Br.WNA. evolved from clade A.Br.TEA tracing it back to strains from Northern France that were assumingly dispatched by European explorers that settled along the St. Lawrence River. Clade B established mostly in Europe along the alpine axis where it evolved in association with local cattle breeds and hence displays specific geographic subclusters. Sequencing technologies are also used for forensic applications to trace unintended or criminal acts of release of B. anthracis. Under natural conditions, B. anthracis generally affects domesticated and wild ruminants in arid ecosystems. The more recently discovered B. cereus biovar anthracis spreads in tropical forests, where it threatens particularly endangered primate populations.
Topics: Animals; Anthrax; Antigens, Bacterial; Bacillus anthracis; Bacterial Toxins; DNA Barcoding, Taxonomic; Genetics, Population; High-Throughput Nucleotide Sequencing; Humans; Molecular Typing; Phylogeny; Phylogeography; Virulence; Virulence Factors
PubMed: 29935338
DOI: 10.1016/j.meegid.2018.06.024 -
Journal of Bacteriology Aug 2021Bis-(3'-5')-cyclic-dimeric GMP (c-di-GMP) is an important bacterial regulatory signaling molecule affecting biofilm formation, toxin production, motility, and virulence....
Bis-(3'-5')-cyclic-dimeric GMP (c-di-GMP) is an important bacterial regulatory signaling molecule affecting biofilm formation, toxin production, motility, and virulence. The genome of Bacillus anthracis, the causative agent of anthrax, is predicted to encode ten putative GGDEF/EAL/HD-GYP-domain containing proteins. Heterologous expression in Bacillus subtilis hosts indicated that there are five active GGDEF domain-containing proteins and four active EAL or HD-GYP domain-containing proteins. Using an mCherry gene fusion-Western blotting approach, the expression of the c-di-GMP-associated proteins was observed throughout the life cycle. Of the six c-di-GMP-associated proteins found to be present in sporulating cells, four (CdgA, CdgB, CdgD, and CdgG) contain active GGDEF domains. The six proteins expressed in sporulating cells are retained in spores in a CotE-independent manner and thus are not likely to be localized to the exosporium layer of the spores. Individual deletion mutations involving the nine GGDEF/EAL protein-encoding genes and one HD-GYP protein-encoding gene did not affect sporulation efficiency, the attachment of the exosporium glycoprotein BclA, or biofilm production. Notably, expression of anthrax toxin was not affected by deletion of any of the determinants. Three determinants encoding proteins with active GGDEF domains were found to affect germination kinetics. This study reveals a spore association of cyclic-di-GMP regulatory proteins and a likely role for these proteins in the biology of the B. anthracis spore. The genus is composed of Gram-positive, rod shaped, soil-dwelling bacteria. As a mechanism for survival in the harsh conditions in soil, the organisms undergo sporulation, and the resulting spores permit the organisms to survive harsh environmental conditions. Although most species are saprophytes, Bacillus cereus and Bacillus anthracis are human pathogens and Bacillus thuringiensis is an insect pathogen. The bacterial c-di-GMP regulatory system is an important control system affecting motility, biofilm formation, and toxin production. The role of c-di-GMP has been studied in the spore-forming bacilli Bacillus subtilis, Bacillus amyloliquefaciens, B. cereus, and B. thuringiensis. However, this regulatory system has not heretofore been examined in the high-consequence zoonotic pathogen of this genus, B. anthracis.
Topics: Antigens, Bacterial; Bacillus anthracis; Bacterial Proteins; Bacterial Toxins; Cyclic GMP; Gene Expression Regulation, Bacterial; Protein Domains; Spores, Bacterial
PubMed: 34096779
DOI: 10.1128/JB.00135-21 -
Molecular Aspects of Medicine Dec 2009Bacillus anthracis is a member of the Bacillus cereus group species (also known as the "group 1 bacilli"), a collection of Gram-positive spore-forming soil bacteria that... (Review)
Review
Bacillus anthracis is a member of the Bacillus cereus group species (also known as the "group 1 bacilli"), a collection of Gram-positive spore-forming soil bacteria that are non-fastidious facultative anaerobes with very similar growth characteristics and natural genetic exchange systems. Despite their close physiology and genetics, the B. cereus group species exhibit certain species-specific phenotypes, some of which are related to pathogenicity. B. anthracis is the etiologic agent of anthrax. Vegetative cells of B. anthracis produce anthrax toxin proteins and a poly-d-glutamic acid capsule during infection of mammalian hosts and when cultured in conditions considered to mimic the host environment. The genes associated with toxin and capsule synthesis are located on the B. anthracis plasmids, pXO1 and pXO2, respectively. Although plasmid content is considered a defining feature of the species, pXO1- and pXO2-like plasmids have been identified in strains that more closely resemble other members of the B. cereus group. The developmental nature of B. anthracis and its pathogenic (mammalian host) and environmental (soil) lifestyles of make it an interesting model for study of niche-specific bacterial gene expression and physiology.
Topics: Animals; Anthrax; Antigens, Bacterial; Bacillus anthracis; Bacterial Capsules; Bacterial Proteins; Bacterial Toxins; Bacteriophages; Conjugation, Genetic; Environment; Gene Expression Regulation, Bacterial; Genome, Bacterial; Phenotype; Plasmids; Soil Microbiology
PubMed: 19654018
DOI: 10.1016/j.mam.2009.07.004 -
Molecular Aspects of Medicine Dec 2009The Bacillus anthracis genome reflects its close genetic ties to Bacillus cereus and Bacillus thuringiensis but has been shaped by its own unique biology and... (Review)
Review
The Bacillus anthracis genome reflects its close genetic ties to Bacillus cereus and Bacillus thuringiensis but has been shaped by its own unique biology and evolutionary forces. The genome is comprised of a chromosome and two large virulence plasmids, pXO1 and pXO2. The chromosome is mostly co-linear among B. anthracis strains and even with the closest near neighbor strains. An exception to this pattern has been observed in a large inversion in an attenuated strain suggesting that chromosome co-linearity is important to the natural biology of this pathogen. In general, there are few polymorphic nucleotides among B. anthracis strains reflecting the short evolutionary time since its derivation from a B. cereus-like ancestor. The exceptions to this lack of diversity are the variable number tandem repeat (VNTR) loci that exist in genic and non genic regions of the chromosome and both plasmids. Their variation is associated with high mutability that is driven by rapid insertion and deletion of the repeats within an array. A notable example is found in the vrrC locus which is homologous to known DNA translocase genes from other bacteria.
Topics: Anthrax; Bacillus anthracis; Chromosomes, Bacterial; DNA, Bacterial; Evolution, Molecular; Genes, Bacterial; Genetic Variation; Genome, Bacterial; Minisatellite Repeats; Phylogeny; Plasmids; Virulence
PubMed: 19729033
DOI: 10.1016/j.mam.2009.08.005 -
Infection, Genetics and Evolution :... Aug 2011Bacillus anthracis, the etiological agent of anthrax, manifests a particular bimodal lifestyle. This bacterial species alternates between short replication phases of... (Review)
Review
Bacillus anthracis, the etiological agent of anthrax, manifests a particular bimodal lifestyle. This bacterial species alternates between short replication phases of 20-40 generations that strictly require infection of the host, normally causing death, interrupted by relatively long, mostly dormant phases as spores in the environment. Hence, the B. anthracis genome is highly homogeneous. This feature and the fact that strains from nearly all parts of the world have been analysed for canonical single nucleotide polymorphisms (canSNPs) and variable number tandem repeats (VNTRs) has allowed the development of molecular epidemiological and molecular clock models to estimate the age of major diversifications in the evolution of B. anthracis and to trace the global spread of this pathogen, which was mostly promoted by movement of domestic cattle with settlers and by international trade of contaminated animal products. From a taxonomic and phylogenetic point of view, B. anthracis is a member of the Bacillus cereus group. The differentiation of B. anthracis from B. cereus sensu stricto, solely based on chromosomal markers, is difficult. However, differences in pathogenicity clearly differentiate B. anthracis from B. cereus and are marked by the strict presence of virulence genes located on the two virulence plasmids pXO1 and pXO2, which both are required by the bacterium to cause anthrax. Conversely, anthrax-like symptoms can also be caused by organisms with chromosomal features that are more closely related to B. cereus, but which carry these virulence genes on two plasmids that largely resemble the B. anthracis virulence plasmids.
Topics: Animals; Bacillus anthracis; Biological Evolution; Host-Pathogen Interactions; Humans; Phylogeny; Phylogeography; Virulence
PubMed: 21640849
DOI: 10.1016/j.meegid.2011.05.013 -
Virulence Dec 2021is an obligate pathogen and a causative agent of anthrax. Its major virulence factors are plasmid-coded; however, recent studies have revealed chromosome-encoded...
is an obligate pathogen and a causative agent of anthrax. Its major virulence factors are plasmid-coded; however, recent studies have revealed chromosome-encoded virulence factors, indicating that the current understanding of its virulence mechanism is elusive and needs further investigation. In this study, we established a silkworm ( infection model of . We showed that silkworms were killed by Sterne and cured of the infection when administered with antibiotics. We quantitatively determined the lethal dose of the bacteria that kills 50% larvae and effective doses of antibiotics that cure 50% infected larvae. Furthermore, we demonstrated that mutants with disruption in virulence genes such as , and had attenuated silkworm-killing ability and reduced colonization in silkworm hemolymph. The silkworm infection model established in this study can be utilized in large-scale infection experiments to identify novel virulence determinants and develop novel therapeutic options against infections.
Topics: Animals; Anthrax; Anti-Bacterial Agents; Bacillus anthracis; Bombyx; Disease Models, Animal; Virulence; Virulence Factors
PubMed: 34490836
DOI: 10.1080/21505594.2021.1965830 -
Clinical Microbiology and Infection :... Aug 2002Anthrax is one of the oldest threats to humankind, and remains endemic in animals in many parts of the world. Human cases are infrequent, and some result from biological... (Review)
Review
Anthrax is one of the oldest threats to humankind, and remains endemic in animals in many parts of the world. Human cases are infrequent, and some result from biological warfare. This review summarizes the current knowledge on the antibacterial activity of available antibiotics. For potential use in the most severe cases of anthrax, antibacterials need to exhibit potent in vitro activity, intracellular bioactivity, and suitable locations in lymph nodes. In animal models, it has been shown that doxycycline and fluoroquinolones are the most active compounds. There is a lack of data for animal models for macrolides and ketolides, some of them exhibiting good in vitro activity. However, systemic anthrax (inhalation or gastrointestinal) is mainly due to anthrax toxin, and therapy directed against intoxication is needed as basic treatment.
Topics: Animals; Anthrax; Anti-Bacterial Agents; Bacillus anthracis; Biological Warfare; Disease Models, Animal; Disease Outbreaks; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 12197869
DOI: 10.1046/j.1469-0691.2002.00527.x -
Emerging Infectious Diseases Oct 2005Pyrosequencing technology is a sequencing method that screens DNA nucleotide incorporation in real time. A set of coupled enzymatic reactions, together with...
Pyrosequencing technology is a sequencing method that screens DNA nucleotide incorporation in real time. A set of coupled enzymatic reactions, together with bioluminescence, detects incorporated nucleotides in the form of light pulses, which produces a profile of characteristic peaks in a pyrogram. We used this technology to identify the warfare agent Bacillus anthracis by sequencing 4 single nucleotide polymorphisms (SNPs) in the rpoB gene as chromosomal markers for B. anthracis. In addition, 1 segment in each of the B. anthracis plasmids pXO1 and pXO2 was analyzed to determine the virulence status of the bacterial strains. Pyrosequencing technology is a powerful method to identify B. anthracis.
Topics: Animals; Bacillus; Bacillus anthracis; Bacterial Typing Techniques; DNA-Directed RNA Polymerases; Genotype; Humans; Plasmids; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Species Specificity; Virulence
PubMed: 16318691
DOI: 10.3201/eid1110.041316 -
Emerging Infectious Diseases Sep 2014
Topics: Animals; Anthrax; Bacillus anthracis; History, 19th Century; Humans; Terminology as Topic
PubMed: 25295335
DOI: 10.3201/eid2009.ET2009