Difference between revisions of "The pathogenesis of Bacillus anthracis"

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==History/Introduction==
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==Overview==
[[Image:bacilli_P7060990 (2).jpg|thumb|300px|right|Anthrax. http://biology.clc.uc.edu/fankhauser/Society/Anthrax/Anthrax.htm].]]
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<b>By [Tony Amolo]</b>
<br>By [Tony Amolo]<br>
 
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[[Image:Bacillus2.jpg|300px|thumb|left|<b>Figure1. Vegetative form of <i>Bacillus Anthracis</i> with stain</b>. http://www.sciencedirect.com/science/article/pii/S0378113509003769].]]<br>Anthrax is an infectious disease caused by the bacteria <i>Bacillus anthracis</i>. <i>Bacillus anthracis</i> is a microorganism from the family <i>Bacillaceae</i>. Figure 1 shows its vegetative form. Unlike other bacillus microorganisms which are harmless saprophytes, <i>Bacillus anthracis</i> is an obligate bacillus pathogen that infects many vertebrates. Based on its physical characteristics, <i>Bacillus anthracis</i> can be categorized with other microorganisms such as <i>Bacillus cereus</i>, <i>Bacillus thuringiensis</i> and <i>Bacillus mycoides</i>. This categorization exists because it is difficult to characterize these organisms based on their 16s rRNA sequences [[#References|[10]]]. Organisms from the bacillus genus are mostly extremophiles. They have the ability to grow in severe conditions which other microorganisms cannot withstand [[#References|[4]]].
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Anthrax is as old as man, it was given its name by a Greek physician named Hippocrates because of the black sore it causes on the skin of human and animals(1). It generally affects warm blooded animals including humans. Aloys Pollender, a German physician who was acknowledged for identifying the disease described <i>Bacillus anthracis</i> as “chyllus corpuscles” after analyzing the abdomen of infected cows that had died of anthrax [[#References|[2]]]. Anthrax was broadly studied in the 1870s by Robert Koch and Louis Pasteur. Koch applied the suspended drop culture method to understand the life cycle of the bacteria and found that the spores formed could survive for long period in harsh environment [[#References|[3]]].Koch’s studies on <i>Bacillus anthracis</i> helped him come up with the germ theory of disease.<br>
  
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==Cell Structure and Metabolism==
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[[Image:Fulton2.jpg|thumb|200px|Right|<b> Figure 2. The spore form of <i>Bacillus Anthracis</i> with Shoeffer Fulton Stain </b>. http://www.sciencedirect.com/science/article/pii/S0378113509003769.]]
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<br> <i>Bacillus anthracis</i> is a gram positive, endospore forming bacteria. Figure 2 shows <i>Bacillus anthracis</i> in its spore form. It is capsulated, immobile and rod shaped. <i>Bacillus anthracis</i> has the ability to make ATP in the presence or absence of oxygen and cannot be seen unless with a microscope. It is  5-6 micrometer long, 1-1.5micrometer wide and  looks like bamboo canes in tissue [[#References|[13]]]. Despite its small size, the diverse abilities of many species of its genus allows them to survive in different environments [[#References|[4]]]. They have the ability to form chains, colonies and biofilms.<br>
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==Habitat and Ecology==
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<br><i>Bacillus anthracis</i> is a soil borne bacteria. It lives best in black steppe soils with lots of  calcium and at pH levels between (7-9). Endemic anthrax areas have been associated with warmer temperatures, higher soil moisture content and topography [[#References|[15]]].<br>
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==Spore Formation, Anatomy and Germination==
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[[Image:neww2.jpg|280px|thumb|left|<b> Figure 3. Transmission Electron Micrograph of <i>Bacillus Anthracis</i> endospore </b>. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC303457/.]]
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<i>Bacillus anthracis</i> forms one endospore per cell. Its spores form when its non reproductive cells are deficient of certain nutrients . The spores are oval in shape and sporulation occurs within 48 hours.
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<i>Bacillus anthracis</i> requires oxygen to sporulate. Spores can tolerate heat, cold, dehydration, radiation and even antibacterials [[#References|[8]]]. The formation of spore commences when cells septate asymmetrically to create a forespore and a mother cell. After septation, the mother cell swallows the forespore and covers it with different layers. The spore is made up of several layers. These layers are the coat, the exosporium and the cortex. Figure 3 reveals these layers through a transmission electron micrograph. The innermost layer is the core. It contains proteins which holds the chromosome. Half of the spore is composed of the spore coat. The flexibility of the spore coat enables the spore to hold the core especially during germination. It protects the spore from harmful chemicals and aids germination. The cortex containing peptidoglycan protects the spore from radiation, heat and makes the core dry. The exosporium is the outermost layer of the spore. It is a protein rich, balloon-like, loose fitting structure covering a spore [[#References|[8]]]. The exosporium has been studied to understand the use of anthrax as a weapon because of its quality and unique structure.
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The disintegration of the mother cell to produce the spore indicates the completion of spore formation.
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The mature spores have a structured arrangement that enables them withstand and endure physical damage and severe environmental conditions. Outside a host, the mature spores of <i>Bacillus anthracis</i> are inactive. Upon entry into a host, they have the ability to germinate and become non reproductive cells that can easily replicate all around the host's internal organs and cause damage.The availability of host’s environment with sufficient nutrients causes germination to occur[[#References|[17]]]. Non reproductive cells transform back to spores whenever the host dies. Germination and growth of spores in the host cells are essential for the release of its virulence factors.
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==Pathogenesis and Virulence factors==
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[[Image:antt2.jpeg|thumb|445px|Right|<b> Figure 4. Mechanism of action of the Anthrax Toxin.</b> http://jama.jamanetwork.com/article.aspx?articleid=194886]]
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<br><i>Bacillus anthracis</i> contains two toxic plasmids: the pX01, which produces the edema factor, the protective antigen and the lethal factor, and the  pX02, which encodes the production of the capsule. <i>Bacillus anthracis</i> carries out its pathogenic process by using its capsule and producing toxics consisting of three proteins(EF, LF and PA)[[#References|[13]]]. The combination of lethal toxin, which constitutes the protective antigen and the lethal factor and edema toxin which constitutes the protective antigen and the edema factor can induce severe cases of the disease [[#References|[7]]]. Out the three factors, the protective antigen plays a crucial  role in the toxic action of <i>Bacillus anthracis</i>. Figure 4 shows the three different ways humans and animals can be exposed to anthrax. It reveals how the toxins of <i>Bacillus anthracis</i> enters the cell. It also indicates other pathogenic mechanisms of the bacteria. Protective antigen  is important in anthrax poisoning because it allows the connection and entry of the lethal factor and Edema factor into the cytosol. It also helps bind the cell receptor, the lethal factor and the edema factor to the host cell. Protective antigen is a primary antigen that exists in anthrax vaccines [[#References|[11]]]. The edema factor is a cyclase that causes an imbalance of water homeostasis. The edema toxin may increase host susceptibility to infection by disrupting the cytokine response of monocytes and by suppressing neutrophil functions [[#References|[11]]]. The lethal factor is a metalloprotease that cleaves major pathways to surface receptors for the transcription of certain genes within the nucleus [[#References|[12]]] while the capsule enhances the virulence by inhibiting the phagocytosis of <i>Bacillus anthracis</i>. <br>
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==Transmission and Prevention==
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[[Image:catt2.jpg|300px|thumb|left|<b> Figure 5. A goat infected by anthrax disease being disposed by burning in Indonesia.</b> http://go.galegroup.com/ps/i.do?id=GALE%7CCX3045200023&v=2.1&u=kenyon&it=r&p=GVRL&sw=w&asid=8b34ef35c63fa98997477f3845a915f4]]
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The common ways of transmission of the anthrax disease are through wounds, the pharynx, gastrointestinal tract, the digestive system after ingesting spore contaminated food or water, skin lesions or abrasions caused by biting flies and the breathing in of air containing anthrax spores. After transmission through one of these route, the spores travel to the lymph nodes where they begin to multiply rapidly and the produce spores which germinate to produce the virulence factors [[#References|[13]]]. The disease can infect humans in 3 different ways namely the cutaneous anthrax, the pulmonary or inhalation anthrax and the gastrointestinal anthrax. Each type of anthrax disease is unique in its method of infection and symptoms. The lethal dose of inhalation anthrax in humans is approximately 8,000 to 10,000 spores, however, scientists have revealed that little dosage inhaled did not cause or show symptoms of the disease [[#References|[23]]]. Transmission of anthrax between animals occurs when infected animals are placed in the same environment as healthy animals. Proper prevention measures in mostly agricultural settings include proper disposal of infected animals, polluted equipment and vaccination. Figure 5 shows how the animal husbandry department of Indonesia tries to prevent the escalation of the disease by burning an infected goat in a pit in October 2004 [[#References|[23]]].<br>
  
<br>Anthrax is a highly contagious disease caused by the bacteria named Bacillus anthracis from the family Bacillaceae. It is the only obligate bacillus pathogen in vertebrates as other Bacillus species are harmless saprophytes. Based on phenotype, it can be classed with Bacillus cereus, Bacillus thuringiensis and Bacillus mycoides as it is difficult to differentiate this group based on their 16S rRNA sequences (10). The genus includes thermophilic, psychrophilic, acidophilic, alkaliphilic, halotolerant, and halophilic, which are capable of growing at temperatures, pH values, and salt concentrations at which few organisms could survive.(4) Named by Hippocrates for the black skin lesions it causes in its cutaneous form, anthrax( Greek: “coal) was well known in the ancient past and is featured in two of the ten plagues of the Old Testament.(1) It generally affects warm blooded animals including humans. Aloys Pollender, who is credited with discovering the disease called the organism “chyllus corpuscles” in the blood spleen, and carbuncle fluid of cows, which had died of the disease (2). Anthrax was extensively studied in the 1870s by Robert Koch and Louis Pasteur. Koch used suspended drop culture methods to trace the complete life cycle of the bacteria and found that the spores formed could remain viable for long period of adverse environments (3). It became a matter of public interest after the bioterrorist attacks in the USA during the autumn of 2001 where five letters containing small quantities of anthrax spores contaminated more than 30,000 people, killed five people and infected 17. (13)<br>
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==Vaccines and Treatment==
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<br>Anthrax was the first bacterial disease for which effective preventive treatment (prophylaxis) was developed [[#References|[11]]]. Prophylaxis played a major role in controlling anthrax in animals and protection to individuals from infection.
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Several vaccines has been produced for the anthrax disease. Louis Pasteur is known as the first microbiologist to produce the first anthrax vaccine in 1881 [[#References|[2]]]. The vaccines were made of spores from weakened genetic variant of <i>Bacillus anthracis</i>. Vaccines produced to combat the disease include non-living vaccines, In vitro protective antigen, Boor and Tresselt vaccine, production in non-proteinaceous media, UK vaccine, American vaccines(Aerobic antigen and Anaerobic antigen) and Russian antigen [[#References|[6]]]. Special therapy can also be  provided to treat anthrax if it is applied immediately to the infected animal or human. Aside from vaccines, antitoxin and antibiotics have been used to treat the disease. Penicillin, ciprofloxacin and doxycycline have been used to treat the susceptible genetic variants of anthrax [[#References|[14]]]. Different methods have been adopted to create an enhanced vaccine for humans. The objective is to develop a vaccine that is non reactogenic and involves little administration to perform efficiently [[#References|[11]]]. However, the difficult aspect of checking the potency of anthrax vaccine is making an assessment in humans. Tests using this pathogenic bacteria is not safe for humans and animals and requires special precautions.<br>
  
==Cell Structure and Metabolism==
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==Application to Bioterrorism==
[[Image:bacilli_P7060990 (2).jpg|thumb|500px|Right|Anthrax. http://biology.clc.uc.edu/fankhauser/Society/Anthrax/Anthrax.htm].]]
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<br>Out of many pathogenic bacteria, <i>Bacillus anthracis</i> is one that can be used for bioterrorism. Of its three types (cutaneous, inhalation and gastrointestinal), inhalation anthrax has been related to bioterrorism because of its mode of transmission. <i>Bacillus anthracis</i> makes a good model  weapon for bioterrorism because its spores can be produced in the laboratory,it survives longer in the environment and can be found easily. Also, because of its small size, it can be placed in food and letters like in 2001 when powdered anthrax spores were mailed to the U.S postal office. Twenty-two cases of anthrax infections were confirmed. Half of these cases involved cutaneous anthrax and no death resulted. The remaining eleven were identified as inhalational anthrax and produced five deaths. Several countries like the past Soviet Union and Iraq have been known to produce <i>Bacillus anthracis</i> as a bioweapon [[#References|[22]]]. Aside from inflicting this pathogenic bacteria through letters, aerosol delivery can also be implemented. It entails aiding the bacteria to travel a longer distance while keeping it odorless and unseen before release by the use of technology [[#References|[22]]]. A global awareness should be created to reject the development of anthrax as weapons and provide a better means to fight this deadly disease. Health Agencies and organizations should emulate the work of agencies such as the Centers for Disease Control and Prevention (CDC), the Federal Bereau of Investigation (FBI) and the World Health Organization (WHO) to find a better understanding of this deadly disease and ensure the safety of human and animal lives, and property. <br>
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==References==
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1] [http://www.sciencedirect.com/science/article/pii/S1286457911002292 Annabel Guicharda, Victor Nizetb, c, Ethan Biera "New insights into the biological effects of anthrax toxins: linking cellular to organismal responses." 2012.]<br><br>
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2] [http://www.sciencedirect.com/science/article/pii/S0738081X0200250X Joseph A Witkowski,Lawrence Charles Parish "The story of anthrax from antiquity to the present: a biological weapon of nature and humans."2002.]<br><br>
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3] [http://www.sciencedirect.com/science/article/pii/S0736467903000799 George Sternbach "The history of anthrax."2003.]<br><br>
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4] [http://www.ncbi.nlm.nih.gov/books/NBK7699/ Peter C. B. Turnbull "Bacillus."1996.]<br><br>
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5] [http://www.sciencedirect.com/science/article/pii/S009829970900048X Maxime Schwartz "Dr. Jekyll and Mr. Hyde: A short history of anthrax."2009.]<br><br>
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6] [http://www.sciencedirect.com/science/article/pii/0264410X84900033 Peter Hambleton, J.Anthony Carman, Jack Melling "Anthrax: the disease in relation to vaccines."1984.]<br><br>
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7] [http://www.sciencedirect.com/science/article/pii/S1369527403001668 Mahtab Moayeri, Stephen H Leppla "The roles of anthrax toxin in pathogenesis."2004.]<br><br>
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8] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1636282/ Jeremy A. Boydston, Ling Yue, John F. Kearney, and Charles L. Turnbough, Jr. "The ExsY Protein Is Required for Complete Formation of the Exosporium of Bacillus anthracis."2006.]<br><br>
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9] [http://www.sciencedirect.com/science/article/pii/S0098299709000727 W. Beyer, P.C.B. Turnbull. "Anthrax in animals."2009.]<br><br>
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10] [http://www.sciencedirect.com/science/article/pii/S1369527400001685 Les Bailliea, , Timothy D Read. "Bacillus anthracis, a bug with attitude!."2001.]<br><br>
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11] [http://www.sciencedirect.com/science/article/pii/S1286457999800045 Stephen F Little, Bruce E Ivins. "Molecular pathogenesis of Bacillus anthracis infection."1999.]<br><br>
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12] [http://www.sciencedirect.com/science/article/pii/S0966842X04002707 Laurence Abrami, Nuria Reig, F. Gisou van der Goot. "Anthrax toxin: the long and winding road that leads to the kill."2005.]<br><br>
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13] [http://www.sciencedirect.com/science/article/pii/S0378113509003769 Antonio Fasanellaa, Domenico Galantea, Giuliano Garofoloa, Martin Hugh Jones. "Anthrax undervalued zoonosis."2010.]<br><br>
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14] [http://www.sciencedirect.com/science/article/pii/S0098299709000612 Martin Hugh-Jonesa, Jason Blackburn. "The ecology of Bacillus anthracis."2009.]<br><br>
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15] [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0072451 Jocelyn C. Mullins, Giuliano Garofolo, Matthew Van Ert, Antonio Fasanella, Larisa Lukhnova, Martin E. Hugh-Jones, Jason K. Blackburn. "Ecological Niche Modeling of Bacillus anthracis on Three Continents: Evidence for Genetic-Ecological Divergence?."2013.]<br><br>
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16] [http://www.cdc.gov/anthrax/]<br><br>
  
<br> Bacillus anthracis is an endospore forming aerobic or facultative anaerobic, rod shaped, immobile and capsulated bacteria. It is a gram positive bacteria but in some cultures may turn gram negative with age  (4). Bacillus anthracis is 1-1.5micrometer wide by 5-6 micrometer in length. They look like bamboo canes in tissue (13). Many species of its genus exhibits a wide range of  abilities that allow them to live in different  natural environment. (4) They have the ability to form only one endospore per cell. These spores are usually formed when vegetative cells are deprived of certain nutrient. Bacillus anthracis requires oxygen to sporulate and its spores are resistant to cold, heat, radiation, desiccation and disinfectants.(8) Spores are oval and sporulation occurs within 48hours. Spore formation begins with asymmetric septation then the mother cell engulfs the forespore and protects it with three layers called the coat, cortex and exosporium. The exosporium is a loose-fitting, balloon-like structure enclosing a spore that has been studied to understand the use of anthrax as a weapon. Concerns about the use of Bacillus anthracis spores as a biological weapon have resulted in efforts to understand the interactions between Bacillus anthracis and the cells of the mammalian immune system, and to develop better detectors for these spores. (8) Bacillus anthracis has been successful as a bioweapon because of its tough resistant endospore and its ability to cause lethal inhalational anthrax.<br>
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17] [http://www.sciencedirect.com/science/article/pii/S0098299709000557 Adam Driks. "The Bacillus anthracis spore."2009.]<br><br>
  
==Habitat and Ecology==
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18] [http://www.fbi.gov/about-us/history/famous-cases/anthrax-amerithrax]<br><br>
<br>Bacillus anthracis is mostly found in the agricultural regions of Central and South America, sub-saharan Africa, central and southwestern Asia, southern and eastern Europe, and the Caribbean. It is a soil borne bacteria. It lives best in black steppe soils especially chernozem and kastanozem, rich in organic matter and calcium at pH levels between (7-9). Endemic anthrax areas have been associated with warmer temperatures, higher soil moisture content and topography (15). Most research suggests that germination and multiplication occurs in the host while spore survival occurs in the soil.<br>
 
  
==Pathogenesis and Virulence factors==
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19] [http://www.sciencedirect.com/science/article/pii/S0098299709000521 Theresa M. Koehler. "Bacillus anthracis physiology and genetics."2009.]<br><br>
<br>Bacillus anthracis depends on two toxic factors from two plasmids:<br>
 
the pX01, 182kb,which encodes the genes for the edema factor (EF), the lethal factor (LF) and the protective antigen (PA), and the <br>
 
pX02, 96kb, which encodes the genes for the biosynthesis of the capsule. Bacillus anthracis expresses it pathogenic action mainly through the capsule and the production of a toxic complex consisting of three proteins(EF, LF and PA). (13) The lethal toxin(LT, the combination of PA and LF) and edema toxin (ET, the combination of PA and EF) are sufficient to produce many of the symptoms of anthrax infection.(7) Of the three factors, the PA plays a fundamental role in the toxic action of Bacillus anthracis. Protective antigen (735 amino acids) plays an important role in anthrax intoxication by mediating the attachment and entry of the lethal factor and Edema factor into the cytosol. It contains regions involved in binding to the cell receptor, binding LF and EF, membrane insertion, and translocation of the anthrax toxin. Protective antigen is a major immunogen present in anthrax vaccines(11). The edema factor(89kDa) is a calcium and calmodulin-dependent adenylate cyclase that causes a dramatic increase in cytoplasmic cAMP leading to an imbalance of water homeostasis. The edema toxin may increase host susceptibility to infection by disrupting the cytokine response of monocytes and by suppressing neutrophil functions (11). The lethal factor is a Zn2+ dependent metalloprotease that cleaves major pathways to surface receptors for the transcription of certain genes within the nucleus(12) while the capsule enhances the virulence by inhibiting the phagocytosis of bacillus anthracis.
 
Anthrax toxins provided a mechanism of trans-membrane translocation of proteins, the discovery of plasmids pXO1 and pXO2 which allowed the study of virulence factors at a genetic level(5). <br>
 
  
==Transmission and Pathology==
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20] [http://www.ncbi.nlm.nih.gov/pubmed/11964119 Nicholson WL. "Roles of Bacillus endospores in the environment."2002.]<br><br>
  
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21] [20] [http://www.ncbi.nlm.nih.gov/pubmed/11964119 Hongbin Liu1, Nicholas H. Bergman, Brendan Thomason, Shamira Shallom, Alyson Hazen, Joseph Crossno, David A. Rasko, Jacques Ravel, Timothy D. Read, Scott N. Peterson, John Yates, and Philip C. Hanna. "Formation and Composition of the Bacillus anthracis Endospore."2003.]<br><br>
  
<br>Bacillus anthracis is not an invasive organism. The most common ways of transmission of the anthrax disease are through micro-wounds, mucous membranes of the mouth, pharynx, gastrointestinal tract, the digestive tract after ingestion of spore contaminated feed or water, skin lesions or abrasions caused by biting flies and the inhalation of dust containing spores. After transmission through one of these route, the spores of Bacillus anthracis are carried from the site of entry to the draining lymph nodes where they begin to multiply rapidly and the produce spores which germinate to produce the virulence factors (13). The pathogenicity of Bacillus anthracis depends on the sensitivity of the host, on the infectious dose(amount of toxin produced), the quality of the capsular coat and the route of penetration (13). Anthrax is not contagious from sick to healthy animals but by the ingestion of spores dispersed into the environment.<br>
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22] [http://jama.jamanetwork.com/article.aspx?articleid=194886 Thomas V. Inglesby, Tara O'Toole, Donald A. Henderson, John G. Bartlett, Michael S. Ascher,Edward Eitzen,MPH; Arthur M. Friedlander, Julie Gerberding, Jerome Hauer,James Hughes, Joseph McDade, Michael T. Osterholm, Gerald Parker,Trish M. Perl, Philip K. Russell,Kevin Tonat, DrPH. "Anthrax as a Biological Weapon, 2002 Updated Recommendations for Management"2002.]<br><br>
  
==Symptoms==
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23] [http://go.galegroup.com/ps/i.do?id=GALE%7CCX3045200023&v=2.1&u=kenyon&it=r&p=GVRL&sw=w&asid=8b34ef35c63fa98997477f3845a915f4 Ed. Brenda Wilmoth Lerner and K. Lee Lerner. "Anthrax."2008.]<br><br>
<br><b>Anthrax in Humans</b>
 
<br><b>Cutaneous anthrax</b>
 
Cutaneous anthrax is also called malignant pustule. It is usually localized around the face, arms, hands, and neck.It  occurs through the contamination of a cut or abrasion that creates an entry for the organism. A primary lesion is formed with a few days and a ring of vesicles develops around the central papule. This dries up to form a black lesion. The lesion develops for 12-14 days leaving a shallow ulcer that heals in 2-3 weeks. Patients show symptoms of headaches, fever of up to 102 degree Fahrenheit, discomfort and even death.  
 
<br><b>Pulmonary(inhalation) anthrax</b>
 
Also known as woolsorter’s disease, pulmonary anthrax is caused by inhaling the anthrax spores. Spores are phagocytosed by alveolar macrophages and transported to the lymph nodes where they germinate and multiply. Fatal bacteraemia and toxaemia then ensue. (10) During the initial stage, the patient experiences mild fever, malaise, fatigue and cough. The second stage include symptoms like acute dyspnea, cyanosis and profuse perspiration
 
<br><b>Gastrointestinal anthrax</b>
 
Also known as splenic fever, gastrointestinal anthrax is extremely rare and occurs mainly in Africa, the Middle East and central and Southern Asia. It is caused by ingestion of insufficiently cooked meat contaminated with spores. Symptoms include diarrhea, ulcer, liver disease and fever.  Another rare form of anthrax in man is anthrax meningitis. (6)<br>
 
  
==Vaccines==
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Edited by student of [mailto:slonczewski@kenyon.edu Joan Slonczewski] for [http://biology.kenyon.edu/courses/biol238/biol238syl09.html BIOL 238 Microbiology], 2009, [http://www.kenyon.edu/index.xml Kenyon College].
<br>Anthrax was the first bacterial disease for which effective preventive treatment (prophylaxis) was developed(11). Prophylaxis played a major role in controlling anthrax in animals and protection to individuals from infection.
 
Several vaccines has been produced for the anthrax disease since Louis Pasteur first produced the attenuated anthrax vaccine in 1881 (2). The vaccines used to fight anthrax are composed of spores from weakened strains of Bacillus anthracis. They are classified into two categories namely;<br>
 
Live attenuated vaccines, capsulated and atoxigenic cap<br>
 
Live attenuated spore vaccines, not capsulated and toxigenic cap. For example, Sterne and sexually transmitted infection (STI) vaccines. (13)<br>
 
Other vaccines include non-living vaccines, In vitro protective antigen, Boor and Tresselt vaccine, production in non-proteinaceous media, UK vaccine, American vaccines(Aerobic antigen and Anaerobic antigen) and Russian antigen (6). Special therapy can also be  provided to treat anthrax if it is applied immediately to the infected animal or human. Aside from vaccines, antitoxin and antibiotics have been used to treat the disease. Several methods have been adopted to create an improved human vaccine. Recombinant DNA methodology is being used to create live vaccine strains of Bacillus anthracis. The aim of the anthrax vaccine create a new vaccine that is safe, non reactogenic, efficacious against all disease and requires a minimum number of inoculations to achieve maximum long lasting immunity (11). The most challenging aspect of evaluating the efficacy of anthrax vaccine is making a logical assessment in humans. Animals can be used as a model but the process can be dangerous.<br>
 
  
==Application to Bioterrorism==
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<!--Do not edit or remove this line-->[[Category:Pages edited by students of Joan Slonczewski at Kenyon College]]
<br>Bacillus anthracis is one of the few pathogenic bacteria that can be used as for bioterrorism. It is most likely to be used because it spores can be produced in the lab,last for a long time in the environment and can be found easily in nature. Also because of its small size, it can be placed in food and letters like in 2001 when powdered anthrax was mailed to the U.S postal office.<br>
 
==References==
 

Latest revision as of 19:02, 8 May 2015

Overview

By [Tony Amolo]

Figure1. Vegetative form of Bacillus Anthracis with stain. http://www.sciencedirect.com/science/article/pii/S0378113509003769].


Anthrax is an infectious disease caused by the bacteria Bacillus anthracis. Bacillus anthracis is a microorganism from the family Bacillaceae. Figure 1 shows its vegetative form. Unlike other bacillus microorganisms which are harmless saprophytes, Bacillus anthracis is an obligate bacillus pathogen that infects many vertebrates. Based on its physical characteristics, Bacillus anthracis can be categorized with other microorganisms such as Bacillus cereus, Bacillus thuringiensis and Bacillus mycoides. This categorization exists because it is difficult to characterize these organisms based on their 16s rRNA sequences [10]. Organisms from the bacillus genus are mostly extremophiles. They have the ability to grow in severe conditions which other microorganisms cannot withstand [4].

Anthrax is as old as man, it was given its name by a Greek physician named Hippocrates because of the black sore it causes on the skin of human and animals(1). It generally affects warm blooded animals including humans. Aloys Pollender, a German physician who was acknowledged for identifying the disease described Bacillus anthracis as “chyllus corpuscles” after analyzing the abdomen of infected cows that had died of anthrax [2]. Anthrax was broadly studied in the 1870s by Robert Koch and Louis Pasteur. Koch applied the suspended drop culture method to understand the life cycle of the bacteria and found that the spores formed could survive for long period in harsh environment [3].Koch’s studies on Bacillus anthracis helped him come up with the germ theory of disease.

Cell Structure and Metabolism

Figure 2. The spore form of Bacillus Anthracis with Shoeffer Fulton Stain . http://www.sciencedirect.com/science/article/pii/S0378113509003769.


Bacillus anthracis is a gram positive, endospore forming bacteria. Figure 2 shows Bacillus anthracis in its spore form. It is capsulated, immobile and rod shaped. Bacillus anthracis has the ability to make ATP in the presence or absence of oxygen and cannot be seen unless with a microscope. It is 5-6 micrometer long, 1-1.5micrometer wide and looks like bamboo canes in tissue [13]. Despite its small size, the diverse abilities of many species of its genus allows them to survive in different environments [4]. They have the ability to form chains, colonies and biofilms.

Habitat and Ecology


Bacillus anthracis is a soil borne bacteria. It lives best in black steppe soils with lots of calcium and at pH levels between (7-9). Endemic anthrax areas have been associated with warmer temperatures, higher soil moisture content and topography [15].

Spore Formation, Anatomy and Germination

Figure 3. Transmission Electron Micrograph of Bacillus Anthracis endospore . http://www.ncbi.nlm.nih.gov/pmc/articles/PMC303457/.

Bacillus anthracis forms one endospore per cell. Its spores form when its non reproductive cells are deficient of certain nutrients . The spores are oval in shape and sporulation occurs within 48 hours. Bacillus anthracis requires oxygen to sporulate. Spores can tolerate heat, cold, dehydration, radiation and even antibacterials [8]. The formation of spore commences when cells septate asymmetrically to create a forespore and a mother cell. After septation, the mother cell swallows the forespore and covers it with different layers. The spore is made up of several layers. These layers are the coat, the exosporium and the cortex. Figure 3 reveals these layers through a transmission electron micrograph. The innermost layer is the core. It contains proteins which holds the chromosome. Half of the spore is composed of the spore coat. The flexibility of the spore coat enables the spore to hold the core especially during germination. It protects the spore from harmful chemicals and aids germination. The cortex containing peptidoglycan protects the spore from radiation, heat and makes the core dry. The exosporium is the outermost layer of the spore. It is a protein rich, balloon-like, loose fitting structure covering a spore [8]. The exosporium has been studied to understand the use of anthrax as a weapon because of its quality and unique structure. The disintegration of the mother cell to produce the spore indicates the completion of spore formation. The mature spores have a structured arrangement that enables them withstand and endure physical damage and severe environmental conditions. Outside a host, the mature spores of Bacillus anthracis are inactive. Upon entry into a host, they have the ability to germinate and become non reproductive cells that can easily replicate all around the host's internal organs and cause damage.The availability of host’s environment with sufficient nutrients causes germination to occur[17]. Non reproductive cells transform back to spores whenever the host dies. Germination and growth of spores in the host cells are essential for the release of its virulence factors.

Pathogenesis and Virulence factors

Figure 4. Mechanism of action of the Anthrax Toxin. http://jama.jamanetwork.com/article.aspx?articleid=194886


Bacillus anthracis contains two toxic plasmids: the pX01, which produces the edema factor, the protective antigen and the lethal factor, and the pX02, which encodes the production of the capsule. Bacillus anthracis carries out its pathogenic process by using its capsule and producing toxics consisting of three proteins(EF, LF and PA)[13]. The combination of lethal toxin, which constitutes the protective antigen and the lethal factor and edema toxin which constitutes the protective antigen and the edema factor can induce severe cases of the disease [7]. Out the three factors, the protective antigen plays a crucial role in the toxic action of Bacillus anthracis. Figure 4 shows the three different ways humans and animals can be exposed to anthrax. It reveals how the toxins of Bacillus anthracis enters the cell. It also indicates other pathogenic mechanisms of the bacteria. Protective antigen is important in anthrax poisoning because it allows the connection and entry of the lethal factor and Edema factor into the cytosol. It also helps bind the cell receptor, the lethal factor and the edema factor to the host cell. Protective antigen is a primary antigen that exists in anthrax vaccines [11]. The edema factor is a cyclase that causes an imbalance of water homeostasis. The edema toxin may increase host susceptibility to infection by disrupting the cytokine response of monocytes and by suppressing neutrophil functions [11]. The lethal factor is a metalloprotease that cleaves major pathways to surface receptors for the transcription of certain genes within the nucleus [12] while the capsule enhances the virulence by inhibiting the phagocytosis of Bacillus anthracis.

Transmission and Prevention

Figure 5. A goat infected by anthrax disease being disposed by burning in Indonesia. http://go.galegroup.com/ps/i.do?id=GALE%7CCX3045200023&v=2.1&u=kenyon&it=r&p=GVRL&sw=w&asid=8b34ef35c63fa98997477f3845a915f4

The common ways of transmission of the anthrax disease are through wounds, the pharynx, gastrointestinal tract, the digestive system after ingesting spore contaminated food or water, skin lesions or abrasions caused by biting flies and the breathing in of air containing anthrax spores. After transmission through one of these route, the spores travel to the lymph nodes where they begin to multiply rapidly and the produce spores which germinate to produce the virulence factors [13]. The disease can infect humans in 3 different ways namely the cutaneous anthrax, the pulmonary or inhalation anthrax and the gastrointestinal anthrax. Each type of anthrax disease is unique in its method of infection and symptoms. The lethal dose of inhalation anthrax in humans is approximately 8,000 to 10,000 spores, however, scientists have revealed that little dosage inhaled did not cause or show symptoms of the disease [23]. Transmission of anthrax between animals occurs when infected animals are placed in the same environment as healthy animals. Proper prevention measures in mostly agricultural settings include proper disposal of infected animals, polluted equipment and vaccination. Figure 5 shows how the animal husbandry department of Indonesia tries to prevent the escalation of the disease by burning an infected goat in a pit in October 2004 [23].

Vaccines and Treatment


Anthrax was the first bacterial disease for which effective preventive treatment (prophylaxis) was developed [11]. Prophylaxis played a major role in controlling anthrax in animals and protection to individuals from infection. Several vaccines has been produced for the anthrax disease. Louis Pasteur is known as the first microbiologist to produce the first anthrax vaccine in 1881 [2]. The vaccines were made of spores from weakened genetic variant of Bacillus anthracis. Vaccines produced to combat the disease include non-living vaccines, In vitro protective antigen, Boor and Tresselt vaccine, production in non-proteinaceous media, UK vaccine, American vaccines(Aerobic antigen and Anaerobic antigen) and Russian antigen [6]. Special therapy can also be provided to treat anthrax if it is applied immediately to the infected animal or human. Aside from vaccines, antitoxin and antibiotics have been used to treat the disease. Penicillin, ciprofloxacin and doxycycline have been used to treat the susceptible genetic variants of anthrax [14]. Different methods have been adopted to create an enhanced vaccine for humans. The objective is to develop a vaccine that is non reactogenic and involves little administration to perform efficiently [11]. However, the difficult aspect of checking the potency of anthrax vaccine is making an assessment in humans. Tests using this pathogenic bacteria is not safe for humans and animals and requires special precautions.

Application to Bioterrorism


Out of many pathogenic bacteria, Bacillus anthracis is one that can be used for bioterrorism. Of its three types (cutaneous, inhalation and gastrointestinal), inhalation anthrax has been related to bioterrorism because of its mode of transmission. Bacillus anthracis makes a good model weapon for bioterrorism because its spores can be produced in the laboratory,it survives longer in the environment and can be found easily. Also, because of its small size, it can be placed in food and letters like in 2001 when powdered anthrax spores were mailed to the U.S postal office. Twenty-two cases of anthrax infections were confirmed. Half of these cases involved cutaneous anthrax and no death resulted. The remaining eleven were identified as inhalational anthrax and produced five deaths. Several countries like the past Soviet Union and Iraq have been known to produce Bacillus anthracis as a bioweapon [22]. Aside from inflicting this pathogenic bacteria through letters, aerosol delivery can also be implemented. It entails aiding the bacteria to travel a longer distance while keeping it odorless and unseen before release by the use of technology [22]. A global awareness should be created to reject the development of anthrax as weapons and provide a better means to fight this deadly disease. Health Agencies and organizations should emulate the work of agencies such as the Centers for Disease Control and Prevention (CDC), the Federal Bereau of Investigation (FBI) and the World Health Organization (WHO) to find a better understanding of this deadly disease and ensure the safety of human and animal lives, and property.

References

1] Annabel Guicharda, Victor Nizetb, c, Ethan Biera "New insights into the biological effects of anthrax toxins: linking cellular to organismal responses." 2012.

2] Joseph A Witkowski,Lawrence Charles Parish "The story of anthrax from antiquity to the present: a biological weapon of nature and humans."2002.

3] George Sternbach "The history of anthrax."2003.

4] Peter C. B. Turnbull "Bacillus."1996.

5] Maxime Schwartz "Dr. Jekyll and Mr. Hyde: A short history of anthrax."2009.

6] Peter Hambleton, J.Anthony Carman, Jack Melling "Anthrax: the disease in relation to vaccines."1984.

7] Mahtab Moayeri, Stephen H Leppla "The roles of anthrax toxin in pathogenesis."2004.

8] Jeremy A. Boydston, Ling Yue, John F. Kearney, and Charles L. Turnbough, Jr. "The ExsY Protein Is Required for Complete Formation of the Exosporium of Bacillus anthracis."2006.

9] W. Beyer, P.C.B. Turnbull. "Anthrax in animals."2009.

10] Les Bailliea, , Timothy D Read. "Bacillus anthracis, a bug with attitude!."2001.

11] Stephen F Little, Bruce E Ivins. "Molecular pathogenesis of Bacillus anthracis infection."1999.

12] Laurence Abrami, Nuria Reig, F. Gisou van der Goot. "Anthrax toxin: the long and winding road that leads to the kill."2005.

13] Antonio Fasanellaa, Domenico Galantea, Giuliano Garofoloa, Martin Hugh Jones. "Anthrax undervalued zoonosis."2010.

14] Martin Hugh-Jonesa, Jason Blackburn. "The ecology of Bacillus anthracis."2009.

15] Jocelyn C. Mullins, Giuliano Garofolo, Matthew Van Ert, Antonio Fasanella, Larisa Lukhnova, Martin E. Hugh-Jones, Jason K. Blackburn. "Ecological Niche Modeling of Bacillus anthracis on Three Continents: Evidence for Genetic-Ecological Divergence?."2013.

16] [1]

17] Adam Driks. "The Bacillus anthracis spore."2009.

18] [2]

19] Theresa M. Koehler. "Bacillus anthracis physiology and genetics."2009.

20] Nicholson WL. "Roles of Bacillus endospores in the environment."2002.

21] [20] Hongbin Liu1, Nicholas H. Bergman, Brendan Thomason, Shamira Shallom, Alyson Hazen, Joseph Crossno, David A. Rasko, Jacques Ravel, Timothy D. Read, Scott N. Peterson, John Yates, and Philip C. Hanna. "Formation and Composition of the Bacillus anthracis Endospore."2003.

22] Thomas V. Inglesby, Tara O'Toole, Donald A. Henderson, John G. Bartlett, Michael S. Ascher,Edward Eitzen,MPH; Arthur M. Friedlander, Julie Gerberding, Jerome Hauer,James Hughes, Joseph McDade, Michael T. Osterholm, Gerald Parker,Trish M. Perl, Philip K. Russell,Kevin Tonat, DrPH. "Anthrax as a Biological Weapon, 2002 Updated Recommendations for Management"2002.

23] Ed. Brenda Wilmoth Lerner and K. Lee Lerner. "Anthrax."2008.

Edited by student of Joan Slonczewski for BIOL 238 Microbiology, 2009, Kenyon College.