Microbiology, pathogenesis, and epidemiology of anthrax
- Kenneth H Wilson, MD
Kenneth H Wilson, MD
- Professor of Medicine, Division of Infectious Diseases
- Duke University Medical Center
Bacillus anthracis, which causes anthrax, was the first clearly recognized bacterial pathogen. The life cycle of the organism was unraveled by Koch, who recognized the importance of dormant anthrax spores in the perpetuation of the organism in soil. These studies eventually helped to underpin Koch's postulates, a milestone in establishing specific pathogens as the causative agents of human and animal diseases. Pasteur created the first successful antibacterial vaccine by successfully attenuating strains of B. anthracis and then proving that these strains could protect sheep from infection with fully virulent strains.
The microbiology, pathogenesis, and epidemiology of anthrax will be reviewed here. The clinical manifestations, diagnosis, treatment, and prevention of anthrax are discussed separately. (See "Clinical manifestations and diagnosis of anthrax" and "Treatment of anthrax" and "Prevention of anthrax".)
B. anthracis is a sporulating gram-positive rod (picture 1). It is nonmotile and grows rapidly at 37ºC on blood agar plates under aerobic conditions. Individual colonies are nonhemolytic and sticky. A gamma bacteriophage can be used to confirm the identity of the organism, and polymerase chain reaction techniques can be used to identify as few as three spores of B. anthracis in a single specimen.
There is less genomic variation in B. anthracis than in any other known bacterial species that causes disease in humans. As a result, strain differentiation relies on demonstrating variations in copy number of tandem repeating DNA segments  or finding single-nucleotide polymorphisms by whole-genome sequencing . B. anthracis is not phylogenetically distinct from Bacillus cereus and is presently considered a clade within the species B. cereus . However, because of its medical significance, B. anthracis retains its original species name.
Portals of entry and dissemination — B. anthracis can invade the body by four routes: gastrointestinal, transcutaneous, pulmonary, and direct parenteral injection.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Andersen GL, Simchock JM, Wilson KH. Identification of a region of genetic variability among Bacillus anthracis strains and related species. J Bacteriol 1996; 178:377.
- Read TD, Salzberg SL, Pop M, et al. Comparative genome sequencing for discovery of novel polymorphisms in Bacillus anthracis. Science 2002; 296:2028.
- Van der Auwera GA, Feldgarden M, Kolter R, Mahillon J. Whole-Genome Sequences of 94 Environmental Isolates of Bacillus cereus Sensu Lato. Genome Announc 2013; 1.
- Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH. Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979. Proc Natl Acad Sci U S A 1993; 90:2291.
- Tonry JH, Popov SG, Narayanan A, et al. In vivo murine and in vitro M-like cell models of gastrointestinal anthrax. Microbes Infect 2013; 15:37.
- Centers for Disease Control and Prevention (CDC). Gastrointestinal anthrax after an animal-hide drumming event - New Hampshire and Massachusetts, 2009. MMWR Morb Mortal Wkly Rep 2010; 59:872.
- Zakowska D, Bartoszcze M, Niemcewicz M, et al. New aspects of the infection mechanisms of Bacillus anthracis. Ann Agric Environ Med 2012; 19:613.
- DRUETT HA, HENDERSON DW, PACKMAN L, PEACOCK S. Studies on respiratory infection. I. The influence of particle size on respiratory infection with anthrax spores. J Hyg (Lond) 1953; 51:359.
- Dalldorf FG, Kaufmann AF, Brachman PS. Woolsorters' disease. An experimental model. Arch Pathol 1971; 92:418.
- Brachman PS. Inhalation anthrax. Ann N Y Acad Sci 1980; 353:83.
- Ringertz SH, Høiby EA, Jensenius M, et al. Injectional anthrax in a heroin skin-popper. Lancet 2000; 356:1574.
- Moayeri M, Leppla SH, Vrentas C, et al. Anthrax Pathogenesis. Annu Rev Microbiol 2015; 69:185.
- Ebrahimi CM, Kern JW, Sheen TR, et al. Penetration of the blood-brain barrier by Bacillus anthracis requires the pXO1-encoded BslA protein. J Bacteriol 2009; 191:7165.
- Kern J, Schneewind O. BslA, the S-layer adhesin of B. anthracis, is a virulence factor for anthrax pathogenesis. Mol Microbiol 2010; 75:324.
- Wang Y, Wei Y, Yuan S, et al. Bacillus anthracis S-layer protein BslA binds to extracellular matrix by interacting with laminin. BMC Microbiol 2016; 16:183.
- Dixon TC, Meselson M, Guillemin J, Hanna PC. Anthrax. N Engl J Med 1999; 341:815.
- Hammerstrom TG, Roh JH, Nikonowicz EP, Koehler TM. Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling. Mol Microbiol 2011; 82:634.
- Mikesell P, Ivins BE, Ristroph JD, et al. Plasmids, Pasteur, and anthrax. ASM News 1983; 7:320.
- Bradley KA, Mogridge J, Mourez M, et al. Identification of the cellular receptor for anthrax toxin. Nature 2001; 414:225.
- Scobie HM, Rainey GJ, Bradley KA, Young JA. Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proc Natl Acad Sci U S A 2003; 100:5170.
- Ramachandran G, Gade P, Tsai P, et al. Potential role of autophagy in the bactericidal activity of human PMNs for Bacillus anthracis. Pathog Dis 2015; 73:ftv080.
- Singh Y, Klimpel KR, Arora N, et al. The chymotrypsin-sensitive site, FFD315, in anthrax toxin protective antigen is required for translocation of lethal factor. J Biol Chem 1994; 269:29039.
- Mogridge J, Cunningham K, Lacy DB, et al. The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen. Proc Natl Acad Sci U S A 2002; 99:7045.
- Blaustein RO, Koehler TM, Collier RJ, Finkelstein A. Anthrax toxin: channel-forming activity of protective antigen in planar phospholipid bilayers. Proc Natl Acad Sci U S A 1989; 86:2209.
- Arora N, Leppla SH. Residues 1-254 of anthrax toxin lethal factor are sufficient to cause cellular uptake of fused polypeptides. J Biol Chem 1993; 268:3334.
- Duesbery NS, Webb CP, Leppla SH, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 1998; 280:734.
- Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci U S A 1982; 79:3162.
- Leppla SH. Bacillus anthracis calmodulin-dependent adenylate cyclase: chemical and enzymatic properties and interactions with eucaryotic cells. Adv Cyclic Nucleotide Protein Phosphorylation Res 1984; 17:189.
- During RL, Li W, Hao B, et al. Anthrax lethal toxin paralyzes neutrophil actin-based motility. J Infect Dis 2005; 192:837.
- Weiner ZP, Ernst SM, Boyer AE, et al. Circulating lethal toxin decreases the ability of neutrophils to respond to Bacillus anthracis. Cell Microbiol 2014; 16:504.
- O'Brien J, Friedlander A, Dreier T, et al. Effects of anthrax toxin components on human neutrophils. Infect Immun 1985; 47:306.
- Barson HV, Mollenkopf H, Kaufmann SH, Rijpkema S. Anthrax lethal toxin suppresses chemokine production in human neutrophil NB-4 cells. Biochem Biophys Res Commun 2008; 374:288.
- Crawford MA, Aylott CV, Bourdeau RW, Bokoch GM. Bacillus anthracis toxins inhibit human neutrophil NADPH oxidase activity. J Immunol 2006; 176:7557.
- Park JM, Greten FR, Li ZW, Karin M. Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science 2002; 297:2048.
- Alileche A, Serfass ER, Muehlbauer SM, et al. Anthrax lethal toxin-mediated killing of human and murine dendritic cells impairs the adaptive immune response. PLoS Pathog 2005; 1:e19.
- Fink SL, Bergsbaken T, Cookson BT. Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci U S A 2008; 105:4312.
- Nguyen CT, Shetty V, Maresso AW. Global metabolomic analysis of a mammalian host infected with Bacillus anthracis. Infect Immun 2015; 83:4811.
- KEPPIE J, SMITH H, HARRIS-SMITH PW. The chemical basis of the virulence of Bacillus anthracis. III. The role of the terminal bacteraemia in death of guinea-pigs from anthrax. Br J Exp Pathol 1955; 36:315.
- Hanna P. Lethal toxin actions and their consequences. J Appl Microbiol 1999; 87:285.
- Firoved AM, Miller GF, Moayeri M, et al. Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice. Am J Pathol 2005; 167:1309.
- Liu S, Zhang Y, Moayeri M, et al. Key tissue targets responsible for anthrax-toxin-induced lethality. Nature 2013; 501:63.
- Beall FA, Dalldorf FG. The pathogenesis of the lethal effect of anthrax toxin in the rat. J Infect Dis 1966; 116:377.
- Hicks CW, Li Y, Okugawa S, et al. Anthrax edema toxin has cAMP-mediated stimulatory effects and high-dose lethal toxin has depressant effects in an isolated perfused rat heart model. Am J Physiol Heart Circ Physiol 2011; 300:H1108.
- Lehmann M, Noack D, Wood M, et al. Lung epithelial injury by B. anthracis lethal toxin is caused by MKK-dependent loss of cytoskeletal integrity. PLoS One 2009; 4:e4755.
- Cui X, Li Y, Li X, et al. Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model. J Infect Dis 2007; 195:572.
- Doolan DL, Freilich DA, Brice GT, et al. The US capitol bioterrorism anthrax exposures: clinical epidemiological and immunological characteristics. J Infect Dis 2007; 195:174.
- Hadler JL. Learning from the 2001 anthrax attacks: immunological characteristics. J Infect Dis 2007; 195:163.
- Boyer AE, Quinn CP, Beesley CA, et al. Lethal factor toxemia and anti-protective antigen antibody activity in naturally acquired cutaneous anthrax. J Infect Dis 2011; 204:1321.
- Titball RW, Turnbull PC, Hutson RA. The monitoring and detection of Bacillus anthracis in the environment. Soc Appl Bacteriol Symp Ser 1991; 20:9S.
- Braun P, Grass G, Aceti A, et al. Microevolution of Anthrax from a Young Ancestor (M.A.Y.A.) Suggests a Soil-Borne Life Cycle of Bacillus anthracis. PLoS One 2015; 10:e0135346.
- Programme on Infectious Disease and Vaccine Sciences, ICDDR,B and Institute of Epidemiology, Disease Control and Research (IEDCR), Ministry of Health and Family Welfare, Department of Livestock Services (DLS), Government of the People's Republic of Bangladesh. Cutaneous anthrax outbreaks in two districts of North-Western Bangladesh, August-October 2009. Health and Science Bulletin December 2009. Bangladesh: International Centre for Diarrhoeal Disease Research, 2009. http://www.icddrb.org/what-we-do/publications/cat_view/52-publications/10042-icddrb-periodicals/10048-health-and-science-bulletin-bangla-and-english/10261-vol-7-no-4-english-2009/11766-cutaneous-anthrax-outbreaks-in-two-districts-of-north-western-bangladesh-august-october-2009 (Accessed on January 16, 2012).
- Navdarashvili A, Doker TJ, Geleishvili M, et al. Human anthrax outbreak associated with livestock exposure: Georgia, 2012. Epidemiol Infect 2016; 144:76.
- Chen WJ, Lai SJ, Yang Y, et al. Mapping the Distribution of Anthrax in Mainland China, 2005-2013. PLoS Negl Trop Dis 2016; 10:e0004637.
- Patassi AA, Saka B, Landoh DE, et al. Detection and management of the first human anthrax outbreak in Togo. Trop Doct 2016; 46:129.
- Hendricks KA, Wright ME, Shadomy SV, et al. Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014; 20.
- Brachman PS. Human anthrax in the United States. Antimicrob Agents Chemother (Bethesda) 1965; 5:111.
- Suffin SC, Carnes WH, Kaufmann AF. Inhalation anthrax in a home craftsman. Hum Pathol 1978; 9:594.
- Centers for Disease Control and Prevention (CDC). Human anthrax associated with an epizootic among livestock--North Dakota, 2000. MMWR Morb Mortal Wkly Rep 2001; 50:677.
- Centers for Disease Control and Prevention (CDC). Inhalation anthrax associated with dried animal hides--Pennsylvania and New York City, 2006. MMWR Morb Mortal Wkly Rep 2006; 55:280.
- Centers for Disease Control and Prevention (CDC). Cutaneous anthrax associated with drum making using goat hides from West Africa--Connecticut, 2007. MMWR Morb Mortal Wkly Rep 2008; 57:628.
- Klempner MS, Talbot EA, Lee SI, et al. Case records of the Massachusetts General Hospital. Case 25-2010. A 24-year-old woman with abdominal pain and shock. N Engl J Med 2010; 363:766.
- Health Protection Scotland. An outbreak of anthrax among drug users in Scotland, December 2009 to December 2010. A report on behalf of the National Anthrax Outbreak Control Team. http://www.documents.hps.scot.nhs.uk/giz/anthrax-outbreak/anthrax-outbreak-report-2011-12.pdf (Accessed on January 16, 2012).
- Price EP, Seymour ML, Sarovich DS, et al. Molecular epidemiologic investigation of an anthrax outbreak among heroin users, Europe. Emerg Infect Dis 2012; 18:1307.
- Berger T, Kassirer M, Aran AA. Injectional anthrax - new presentation of an old disease. Euro Surveill 2014; 19.
- Inverarity DJ, Forrester VM, Cumming JG, et al. Injectional anthrax at a Scottish district general hospital. Epidemiol Infect 2015; 143:1311.
- Keim P, Grunow R, Vipond R, et al. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years. EBioMedicine 2015; 2:1613.
- Notice to readers: Ongoing investigation of anthrax--Florida, October 2001. MMWR Morb Mortal Wkly Rep 2001; 50:877.
- Bush LM, Abrams BH, Beall A, Johnson CC. Index case of fatal inhalational anthrax due to bioterrorism in the United States. N Engl J Med 2001; 345:1607.
- Centers for Disease Control and Prevention (CDC). Update: Investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep 2001; 50:889.
- Centers for Disease Control and Prevention (CDC). Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep 2001; 50:909.
- Centers for Disease Control and Prevention (CDC). Update: Investigation of bioterrorism-related anthrax--Connecticut, 2001. MMWR Morb Mortal Wkly Rep 2001; 50:1077.
- Jernigan DB, Raghunathan PL, Bell BP, et al. Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Emerg Infect Dis 2002; 8:1019.
- Weis CP, Intrepido AJ, Miller AK, et al. Secondary aerosolization of viable Bacillus anthracis spores in a contaminated US Senate Office. JAMA 2002; 288:2853.
- Bhattacharjee Y. FBI Anthrax Investigation Under Scientific Review, May 6, 2009. Science Insider. http://blogs.sciencemag.org/scienceinsider/2009/05/fbi-anthrax-inv.html (Accessed on June 09, 2009).
- Bush LM, Perez MT. The anthrax attacks 10 years later. Ann Intern Med 2012; 156:41.
- Centers for Disease Control and Prevention (CDC). Suspected cutaneous anthrax in a laboratory worker--Texas, 2002. MMWR Morb Mortal Wkly Rep 2002; 51:279.
- Centers for Disease Control and Prevention. CDC lab incident: Anthrax. https://www.cdc.gov/anthrax/news-multimedia/lab-incident/index.html (Accessed on October 31, 2017).
- Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science 1994; 266:1202.
- Sahl JW, Pearson T, Okinaka R, et al. A Bacillus anthracis Genome Sequence from the Sverdlovsk 1979 Autopsy Specimens. MBio 2016; 7.