Gram Negative Bacteria as possible agents of bioterroism

Botulism: C. botulinum produce botulinum toxins, proteins of MW of about 150,000 which are the most toxic compounds known. There are 7 distinct neurotoxins, A through G, produced by different strains of the bacillus. As a biological weapon, botulinum toxins may be aierosolized or used to sabotage food supplies. The totulinum toxins produce a blockage of acetylcholine release. They are zinc-dependent endopeptidases that cleave polypeptides essential for docking of synaptic vesicles to the presynaptic membrane of the nerve terminal. The mouose-bioassay is the classic test. Competitive RT-PCR, which meansures the elvel of toxin-encoidng mRNA in C. botulinum is more rapid and sensitive.

Burkholderia: Due to their antibiotic resistance and the high motality rate from their associated diseases, B. mallei and B. pseudomallei are considered to be potential biological ware agents. 

Escherichia coli O157:H7 and other Shiga toxin-producing E. coli (STEC) has emerged recently as important human pathogens causing bloody diarrhea and haemolytic uremic syndrom. Because of morbidity and mortablity associated with outbreaks and sporadic cases of STEC diseases, these pathgoens are considered a major public health concern worldwide. E. coli O157:H7 is the serotype most frequently isolated form patients, but STEC strains of other serotypes have also been reproted. These pathgoens share different virulence factors including a pathogenicity island (LEE) encoding proteins responsible for the intimate adherance of STEC to epithelial cells and the production of the toxins, Stx1 and Stx2.

Salmonella was already used by a religious sect to infect 751 individuals in Oregon through 10 salad bars in an attempt to sway local political elections (1997).

Tularemia: F. tularensis is a small, nonmotiel, aerobic gram-negative coccobacillus, which causes tularemia. Human usually acquire tularemia (also known as rabbit.

Plague (Y. pestis): During the pandemic starting in 1346, plague, also known as the black death or great pestilence, killed 20-30 million Europeans. Plague is an enzootic infection of rats, ground squirrels, prairi dogs, and other rodents, and human plague occurs typically when plague-infected fleas bite humans, who then develop bubonic plague. Outbreaks of plague in China are attributed to plague-infected fleas dropped by a secret branch of the Japanese army during World War II. The U.S. and Soviet Union developed techniques to directly aerosolize plague particles that cuase pneumonic plauge, a highly lethal and potentially contagious form.

Gram Positive Bacteria as possible agents of bioterrorism

Anthrax (Bacillus anthracis): is an aerobic spore-forming, gram-positive rod, which causes anthrax. Anthrax spores are very resistant and may remain dormant in the soil for decades. In 1970, a report of the World Health Organization (WHO) estimated that the release of 50 kg of anthrax spores along a 2-km line upwind of a city of 500,000 would result in 95,000 deaths and a 2993 report of the U.S. Congressional Office of Technology Assessment predicted that release of 100 kg of anthrax spores upwind of Washington, DC, would result in 130,000 to 3 million deaths. 

The toxin ofBacillus anthracisis used in biological warfare and bioterrorism. During the 20th century anthrax was used as a weapon in many countries. It has also been directed toward farm animals for warfare. The significance of anthrax as a terror weapon was realized in 2001. Although small outbreaks can result in a strong response, some people argue that anthrax is not an ideal biological weapon because the organism is not particularly pathogenic. To infect people, a large number of spores are needed. The most effective form of anthrax is a very fine powder. Therefore, to make anthrax a weapon, the preparation needs to be ground into a fine powder. Anticaking agents are necessary as well to prevent clumping of the spores. See Microbe Wiki

The route of spore entry into the host dictates the specific pathology and severity of the disease; e.g., cutaneous anthrax is generally far less severe than either the gastrointestinal or inhalational form. Endospores are produced in response to nutrient deprivation via an alternative developmental cascade by two known genera of gram-positive bacteria, Clostridium and Bacillus. During sporulation, vegetative metabolism is minimized, and a series of alternative sigma factors are sequentially expressed and activated to coordinate the expression of mRNAs responsible for spore development. Spore germination, outgrowth, and initiation of a vegetative cycle occur when small molecules, often nutrients and/or ions, are sensed in the context of aqueous environments. B. anthracis spores recognize specific signals provided by the local environment of a mammalian host and rapidly germinate when associated with the host cells that engulf them. Host signals that induce B. anthracis germination include specific amino acids and nucleoside combinations that are recognized by a family of gerA-like sensor operons. Activation of the germinant sensors is believed to be the initiating event of germination. Processes that follow involve hydration of the core, expulsion of cations and dipicolinic acid, breakup of the cortex, and onset of vegetative metabolism, including production of potent virulence factors.  See Liu

There exists a vaccine for anthrax. See FDA 

Viruses as possible agents of bioterrorism

Small pox (variola major): is a member of the genus orthopoxvirus, which also includes monkeypox, cowpox, and vaccinia. The viruses are complex, and the virion is breack-shaped with a diameter of about 200 mm. Spread from person to person occurs via aerosols expelled from the ororpharynx of infected persons, by direct contact, or via contaminated clothing or bed lines. After multiplication of virus in the spleen, bone marrow, and lymph nodes, a secondary viremia begins on about the 8th day and is followed by fever and toxemia. In the US, about 140,000 vials of vaccine are stored at the CDC, and it is estimated that about 50 to 100 million doses are available world-wide. Poxviruses are considered to be among the most dangerous microorganisms that might be used for a bioterrorist attack. See CDC

Smallpox was used as a biological weapon during the French and Indian Wars, (1754 to 1767) when British soldiers distributed smallpox-infected blankets to American Indians. In the 1980s, the Soviet Union developed variola as an aerosol biological weapon and produced tons of virus-laden material intended for release via intercontinental ballistic missiles. See Johns Hopkins

Thousands of years ago, variola virus (smallpox virus) emerged and began causing illness and deaths in human populations, with smallpox outbreaks occurring from time to time. Thanks to the success of vaccination, the last natural outbreak of smallpox in the United States occurred in 1949. In 1980, the World Health Assembly declared smallpox eradicated (eliminated), and no cases of naturally occurring smallpox have happened since.  See CDC

Viral hemorrhagic fever (VHF): describes diseases caused by several RNA viruses from Filoviridae (Ebola and Marburg), Arenaviridae (Junin, Lassa, Machup, Guanarito), Bunyaviridae (Nairovirus, Phlebovirus, Hantavirus), andFlaviviridae (yellow fever virus, Dengue viruses, Kyasanur Forest Disease virus, Omsk hemorrhagic fever virus) families.

Toxins as possible agents of bioterrorism

Ricin:

The CDC classifies ricin as a category B biological agent, placing it among high priority toxins and pathogens that are moderately easy to disseminate, result in moderte mobidity rates and low mortality rates, and require specific enhancements of CDCs diagnostic capacity and enhanced disease surveillance. 

Ricin is a toxin that is an inhibitor of protein synthesis, produced by a shrub of the family Euphorbiaceae, the castor-oil plant. It is a very toxic glycoprotein which is formed from two polypeptide chains A and B, joined together by a disulfide bridge. The B-chain is a lectin which binds to glycoproteins containing galactose and to glycolipids expressed on the cell surface, facilitating the entry of ricin into the cytosol. The A-chain inhibits protein synthesis by irreversibly inactivating the 28S ribosomal subunit. Ricin is toxic by the oral, parenteral, and pulmonary route. Ricin dispersed in the form of powder or aerosol can cause, after a period varying from a few minutes to several hours, signs of irritation of the eyes and the pharynx. The following antidotes can be used: analogs of sugar that prevent ricin from binding to its target or inhibitors of the catalytic subunit such as azidothymidine. Another strategy for the treatment of ricin poisoning is vaccination.

Ricin comprises tow glycoprotein chains (A and B) joined by a disulfide bond. The B chain can bind to cell surface antigens enabling the molecule’s uptake. Cellular processes disrupt the disulfide bond and releases the A chain, which functions as a ribosome inactivating protein or an RIP. Ribosomes perfomr protein synthesis. A chain release disrupts that rpcoess, leading to the poisonous effects that a patient experiences.