Anthrax characterized

The advent of immunoproteomics made possible the identification of highly immunogenic proteins that can be used for vaccine development. Proteins that have the greatest potential for eliciting a protective immune response are collectively referred to as the pathogen s immunome. Immunoproteomics has been utilized to characterize the immu-nome of B. anthracis for the development of a safer and equally efficacious vaccine. The immunoreactive proteins are first identified by using 2DE Western blot analysis in conjunction with mass spectrometry. In B. anthracis, for example, antisera from humans post-infected with anthrax were used to probe Western blots of its various... 

The symptoms of oropharyngeal anthrax include swelling of the neck, and lesions in the oral cavity (similar to cutaneous lesions), sometimes on the tonsils. Other symptoms include fever, swollen lymph nodes, and inability to swallow. Shock and toxemia can characterize both forms of the disease. The fatality rate for gastrointestinal anthrax ranges from 25 to 60%.3... 

Classical bacterial exotoxins, such as diphtheria toxin, cholera toxin, clostridial neurotoxins, and the anthrax toxins are enzymes that modify their substrates within the cytosol of mammalian cells. To reach the cytosol, these toxins must first bind to different cell-surface receptors and become subsequently internalized by the cells. To this end, many bacterial exotoxins contain two functionally different domains. The binding (B-) domain binds to a cellular receptor and mediates uptake of the enzymatically active (A-) domain into the cytosol, where the A-domain modifies its specific substrate (see Figure 1). Thus, three important properties characterize the mode of action for any AB-type toxin selectivity, specificity, and potency. Because of their selectivity toward certain cell types and their specificity for cellular substrate molecules, most of the individual exotoxins are associated with a distinct disease. Because of their enzymatic nature, placement of very few A-domain molecules in the cytosol will normally cause a cytopathic effect. Therefore, bacterial AB-type exotoxins which include the potent neurotoxins from Clostridium tetani and C. botulinum are the most toxic substances known today. However, the individual AB-type toxins can greatly vary in terms of subunit composition and enzyme activity (see Table 2). 

Signs and symptoms of inhalational anthrax follow a biphasic course. The initial phase is characterized by fever, malaise, and unproductive cough characteristic of an upper respiratory infection. Following this flu-like phase, the patient will typically recover after 2-4 days. The second phase proceeds rapidly with the following constellation of signs and symptoms acute dyspnea, pleural effusion, fever, progressively worsening respiratory failure, cyanosis, circulatory collapse, shock, and death, if left untreated. 

Inactivated anthrax vaccine is mainly used for protection against occupational anthrax exposure. A complete vaccine series consists of three 0.5-ml subcutaneous doses at 2-week intervals, followed by three additional doses 6, 12, and 18 months after the first dose. Mild local reactions occur in 30% of vacci-nees, including local erythema and tenderness, which occurs within 24 hours and begins to subside within 48 hours. The reactions tend to increase in severity by the fifth injection. Systemic reactions are rare and usually characterized by malaise and lassitude, chills, and fever (1). 

When anthrax spores enter the body, particularly when inhaled or ingested, they immediately become active, multiply, and release a three-part protein toxin, of which one part is deadly to humans and is referred to as the lethal factor. The lethal factor interferes with the body s ability to mount an immune response. Cutaneous (skin) infection with anthrax is rarely fatal if treated. Initial symptoms of cutaneous anthrax infection appear within days of exposure, beginning with an itchy bump that develops into a black sore, sometimes accompanied by flulike symptoms. Anthrax infection via ingestion (e.g., via contaminated food) causes food poisoning-like symptoms and may be fatal if untreated. Inhalational exposure to anthrax is the most serious form and is characterized by mild respiratory symptoms that develop into severe symptoms, breathing difficulties, shock, and eventually death if not treated. Typically symptoms appear within a week of exposure to infective B. anthracis but may not appear for 2 months (Inglesby et al. 2002). 

Uchida I, Hornung JM, Thorne CB, Klimpel KR, Leppla SH. Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis. J Bacteriol. 1993 175 5329-5338. 

The intestinal disease form of anthrax may follow the consumption of contaminated food and is characterized by an acute inflammation of the intestinal tract. Initial signs of nausea, lo.ss of appetite, vomiting, and fever are followed by abdominal pain, vomiting of blood, and severe diarrhea. 

---