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Microbiology Spectrum May 2019The group includes several species with closely related phylogeny. The most well-studied members of the group, , , and , are known for their pathogenic potential.... (Review)
Review
The group includes several species with closely related phylogeny. The most well-studied members of the group, , , and , are known for their pathogenic potential. Here, we present the historical rationale for speciation and discuss shared and unique features of these bacteria. Aspects of cell morphology and physiology, and genome sequence similarity and gene synteny support close evolutionary relationships for these three species. For many strains, distinct differences in virulence factor synthesis provide facile means for species assignment. is the causative agent of anthrax. Some strains are commonly recognized as food poisoning agents, but strains can also cause localized wound and eye infections as well as systemic disease. Certain strains are entomopathogens and have been commercialized for use as biopesticides, while some strains have been reported to cause infection in immunocompromised individuals. In this article we compare and contrast , , and , including ecology, cell structure and development, virulence attributes, gene regulation and genetic exchange systems, and experimental models of disease.
Topics: Animals; Anthrax; Anthrax Vaccines; Bacillus; Bacillus anthracis; Bacillus cereus; Bacillus thuringiensis; Bacterial Toxins; Bacterial Vaccines; Biological Control Agents; DNA, Bacterial; Disease Models, Animal; Ecology; Gastrointestinal Diseases; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genome, Bacterial; Humans; Infections; Invertebrates; Phylogeny; Species Specificity; Spores, Bacterial; Virulence
PubMed: 31111815
DOI: 10.1128/microbiolspec.GPP3-0032-2018 -
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 -
Emerging Infectious Diseases Sep 2014
Topics: Animals; Anthrax; Bacillus anthracis; History, 19th Century; Humans; Terminology as Topic
PubMed: 25295335
DOI: 10.3201/eid2009.ET2009 -
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 -
ACS Infectious Diseases Mar 2022The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of... (Review)
Review
The paradigm of antivirulence therapy dictates that bacterial pathogens are specifically disarmed but not killed by neutralizing their virulence factors. Clearance of the invading pathogen by the immune system is promoted. As compared to antibiotics, the pathogen-selective antivirulence drugs hold promise to minimize collateral damage to the beneficial microbiome. Also, selective pressure for resistance is expected to be lower because bacterial viability is not directly affected. Antivirulence drugs are being developed for stand-alone prophylactic and therapeutic treatments but also for combinatorial use with antibiotics. This Review focuses on drug modalities that target bacterial exotoxins after the secretion or release-upon-lysis. Exotoxins have a significant and sometimes the primary role as the disease-causing virulence factor, and thereby they are attractive targets for drug development. We describe the key pre-clinical and clinical trial data that have led to the approval of currently used exotoxin-targeted drugs, namely the monoclonal antibodies bezlotoxumab (toxin B/TcdB, ), raxibacumab (anthrax toxin, ), and obiltoxaximab (anthrax toxin, ), but also to challenges with some of the promising leads. We also highlight the recent developments in pre-clinical research sector to develop exotoxin-targeted drug modalities, i.e., monoclonal antibodies, antibody fragments, antibody mimetics, receptor analogs, neutralizing scaffolds, dominant-negative mutants, and small molecules. We describe how these exotoxin-targeted drug modalities work with high-resolution structural knowledge and highlight their advantages and disadvantages as antibiotic alternatives.
Topics: Anti-Bacterial Agents; Bacillus anthracis; Bacterial Toxins; Clostridioides difficile; Exotoxins
PubMed: 35099182
DOI: 10.1021/acsinfecdis.1c00296 -
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 -
Trends in Molecular Medicine Mar 2015Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and... (Review)
Review
Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection.
Topics: Animals; Anthrax; B-Lymphocytes; Bacillus anthracis; Disease Models, Animal; Epithelium; Gastrointestinal Diseases; Gastrointestinal Microbiome; Humans
PubMed: 25577136
DOI: 10.1016/j.molmed.2014.12.003 -
Journal of Bacteriology Aug 2018Germination of spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, cannot cause disease pathologies unless its spores... (Review)
Review
Germination of spores is a crucial early requirement for colonization of the gastrointestinal tract. Likewise, cannot cause disease pathologies unless its spores germinate into metabolically active, toxin-producing cells. Recent advances in our understanding of spore germination mechanisms indicate that this process is both complex and unique. This review defines unique aspects of the germination pathways of and compares them to those of two other well-studied organisms, and germination is unique, as does not contain any orthologs of the traditional GerA-type germinant receptor complexes and is the only known sporeformer to require bile salts in order to germinate. While recent advances describing germination mechanisms have been made on several fronts, major gaps in our understanding of germination signaling remain. This review provides an updated, in-depth summary of advances in understanding of germination and potential avenues for the development of therapeutics, and discusses the major discrepancies between current models of germination and areas of ongoing investigation.
Topics: Bacillus anthracis; Bacterial Proteins; Clostridioides difficile; Clostridium Infections; Clostridium perfringens; Humans; Membrane Proteins; Spores, Bacterial
PubMed: 29760211
DOI: 10.1128/JB.00218-18 -
Journal of Bacteriology Nov 2022Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are the major pathogens of the spore-forming genus and possess an outer spore layer, the exosporium, not...
Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are the major pathogens of the spore-forming genus and possess an outer spore layer, the exosporium, not found in many of the nonpathogenic species. The exosporium consists of a basal layer with the ExsY, CotY, and BxpB proteins being the major structural components and an exterior nap layer containing the BclA glycoprotein. During the assembly process, the nascent exosporium basal layer is attached to the spore coat by a protein linker that includes the CotO and CotE proteins. Using transmission electron microscopy, Western blotting, immunofluorescence, and fluorescent fusion protein approaches, we examined the impact of single, double, and triple mutants of the major exosporium proteins on exosporium protein content and distribution. Plasmid-based expression of and resulted in increased production of exosporium lacking spores, and the former also resulted in outer spore coat disruptions. The exosporium bottlecap produced by null spores was found to be more stable than previously reported, and its spore association was partially dependent on CotE. Deletion mutants of five putative spore genes (, , , , and ) were created and shown not to have obvious effects on spore morphology or BclA and BxpB content. The BclC collagen-like glycoprotein was found to be present in the spore and possibly localized to the interspace region. B. anthracis is an important zoonotic animal pathogen causing sporadic outbreaks of anthrax worldwide. Spores are the infectious form of the bacterium and can persist in soil for prolonged periods of time. The outermost B. anthracis spore layer is the exosporium, a protein shell that is the site of interactions with both the soil and with the innate immune system of infected hosts. Although much is known regarding the sporulation process among members of the genus , significant gaps in our understanding of the exosporium assembly process exist. This study provides evidence for the properties of key exosporium basal layer structural proteins. The results of this work will guide future studies on exosporium protein-protein interactions during the assembly process.
Topics: Bacillus anthracis; Spores, Bacterial; Bacterial Proteins; Membrane Glycoproteins; Bacillus; Glycoproteins; Soil
PubMed: 36194010
DOI: 10.1128/jb.00291-22 -
Microbiology Spectrum Aug 2016To survive adverse conditions, some bacterial species are capable of developing into a cell type, the "spore," which exhibits minimal metabolic activity and remains... (Review)
Review
To survive adverse conditions, some bacterial species are capable of developing into a cell type, the "spore," which exhibits minimal metabolic activity and remains viable in the presence of multiple environmental challenges. For some pathogenic bacteria, this developmental state serves as a means of survival during transmission from one host to another. Spores are the highly infectious form of these bacteria. Upon entrance into a host, specific signals facilitate germination into metabolically active replicating organisms, resulting in disease pathogenesis. In this article, we will review spore structure and function in well-studied pathogens of two genera, Bacillus and Clostridium, focusing on Bacillus anthracis and Clostridium difficile, and explore current data regarding the lifestyles of these bacteria outside the host and transmission from one host to another.
Topics: Animals; Anthrax; Bacillus anthracis; Clostridioides difficile; Clostridium Infections; Humans; Spores, Bacterial
PubMed: 27726794
DOI: 10.1128/microbiolspec.VMBF-0029-2015