Transcript General Mode of Infection

Bacillus anthracis
Amanda Russell
Anna Bossert
Taxonomy
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Kingdom: Bacteria
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Bacillus
Species: anthracis
Basic Facts
• Zoonotic Disease: usually
carried by animals, can be
transmitted to human hosts
under natural conditions
• Rod-shaped
• monomorphic
• Endospore-forming, remain
viable in soil and animal
products for decades
• Gram-positive
• Aerobic respiration
• Exotoxin producing
• Grows best at 24-40⁰C
• Incubation period: 1 to 15 days
• Three forms: inhaltion,
gastrointestinal, cutaneous
Virulence Factors
• Encoded on two plasmids
▫ One encodes for the synthesis of a polyglutamyl
capsule (inhibits phagocytosis by macrophages)
▫ Other bears genes encoding for the synthesis of
exotoxins
• Exotoxins: three proteins
▫ Protective antigen
▫ Edema Factor: adenylate cyclase activity, increases
cAMP, leads to cytoplasm loss after forming an edema
▫ Lethal Factor: interferes with transcription factor in
genome (NfkB) which regulates immunity genes. Once
these are no longer transcribed, immune response of
macrophages will fade.
General Mode of Infection
• B. anthracis spores enter the body (lungs, skin
lesion, gastrointestinal) and germinate, giving
rise to the vegetative form
• The bacterium begins to produce capsules
containing exotoxins, which will help evade the
host’s immune system
• The PA portion will bind to receptors on the
membrane of macrophages, when seven
complexes are combined they form a ring. This
ring will pierce through the membrane and the
macrophage will shuttle in the complex as an
endosome
General Mode of Infection cont.
• The PA molecules will form a pore that pierces
the endosome membrane, releasing the EF and
LF into the cytoplasm of the macrophage
• EF and LF essentially kill the macrophage, and
release the contents of the macrophage to the
outside.
• The endosome enzymes that were released will
degrade surrounding tissues, resulting in the
common symptoms of anthrax.
Cutaneous Anthrax
• B. anthracis comes into contact with a skin
lesion, or cut.
• The spores germinate, producing bacteria, which
produce exotoxins to evade the macrophages
• Infection is manifested in a painless ulcer with a
necrotic (dead) center
• Transmission: coming in contact with infected
animals or their products through a skin lesion
Symptoms of cutaneous anthrax
• Boil-like skin lesion forming a
painless ulcer
• Swelling of the lymph glands
• Fever
• Headache
Inhalation Anthrax
• The spores are inhaled and lodge in the alveolar
spaces
• Alveolar macrophages engulf the spores.
• Spores germinate within macrophages after
failed phagocytosis
• Bacteria proceed to lymph nodes and spread into
bloodstream, where they begin to release the
exotoxins
• Transmission: inhaling the spores of B.
anthracis
Symptoms of Inhalation Anthrax
• Initial symptoms: sore throat,
mild fever, muscle aches
• Severe difficulty breathing
• Septic shock
• Development of meningitis
• Respiratory failure resulting in
death
Gastrointestinal Anthrax
• Spores are consumed after eating undercooked meat
• Spores can evade stomach acid due to their capsule
• Once in the digestive tract, they begin to germinate
and produce bacteria, which release exotoxins
• After the macrophages have been lysed, the
endosome enzymes begin degrading intestinal walls,
allowing the bacteria to spread directly into the
bloodstream
• Transmission: Digesting undercooked meat
containing spores
Symptoms of Gastrointestinal anthrax
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Serious gastrointestinal difficulty
Nausea
Fever
Abdominal pain
Vomiting of blood
Severe bloody diarrhea
Acute inflammation of intestinal tract
Loss of appetite
Diagnosis
• A diagnosis can be made by taking a smear of a
skin lesion (if cutaneous anthrax) and gramstaining the sample.
• Blood tests that show encapsulated, broad,
gram-positive bacilli
• Cultures: large, flat, nonhemolytic colonies, nonmotile, will test positive for catalse, positive for
capsule production
• Confirmatory Diagnosis: Serological tests for
toxins at reference laboratories
Transmission
• Bacillus anthracis is transmitted mainly through
the contact of infected animals or their products,
and humans, resulting in cutaneous anthrax
• It cannot be spread from human to human.
• 2001: Anthrax was sent in the form of a powder
in letters, when the recipient of the letter opened
them and inhaled the spores, they became
infected. 5 out of 22 died.
▫ Biological Warfare Debate
Prevalence
• In the past, anthrax was found all over the world.
• Now, this bacterium is found mainly in underdeveloped
countries lacking the means of disease control; such as
the Middle East, Africa, Australia, southern and eastern
Europe, South and Central America, Asia
• It is not common in the United States, although small
outbreaks periodically occur in agricultural areas on
animals.
• The last outbreak resulted in the death of 5 out of 22
people in 2001.
▫ 1987: 20 out of 22 had died
• 2,000 – 20,000 human outbreaks annually
Susceptibility
• All warm-blooded animals are susceptible to
anthrax, especially herbivores
▫ Other domesticated animals such as horses and
mules may also contract the disease.
Treatment
• Cutaneous / gastrointestinal
▫ Antibiotic therapy for 7 – 14 days
• Inhalation
▫ Antibiotic therapy for 30 days if used alone
▫ If vaccine is available, antibiotics can be
discontinued after 3 doses of vaccine
Vaccine
• Anthrax Vaccine Adsorbed (AVA)
▫ 6-dose series at 0,2,4 weeks and 6,12,18 months
▫ Annual booster injections to maintain immunity
• Who receives vaccine?
▫ Animals, mainly cattle
▫ People with high occupational risk
 Military, people close to an outbreak
Prevention
• Decontamination
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Wash down with anti-microbe effective soap
Boil articles that came in contact with infected hosts
Chlorine
Burning articles
• Early detection
▫ USPS installed BioDetection System
• Antibiotics
▫ Penicillin
▫ Doxycycline
Current Research
• New research has found that extracellular
metalloproteases may play a role in the survival
of the bacterium
▫ Aid in degradation of the LL-37 peptide.
▫ Other bacillus species showed no resistance to this
peptide
Current Research cont.
• Anti-protective antigen antibody has been
shown to suppress the vegetative form of B.
anthracis before it sporulates.
Current Research cont.
• Research has also shown a new technique in
identifying anthrax spores before a new
outbreak occurs.
▫ Microwave-Accelerated Metal-Enhanced
Fluorescence (MAMEF) (Metal-enhanced flulow
power microwave heating) is used to accelerate
DNA hybridization
▫ The DNA of the B. anthracis spores was detected
almost immediately.
References
• http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&Ter
mToSearch=17955147&ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubme
d_ResultsPanel.Pubmed_RVDocSum
• Microbiology Lecture Textbook
• http://www.cdc.gov/
• http://www.nlm.nih.gov/medlineplus/anthrax.html
• http://pathport.vbi.vt.edu/pathinfo/pathogens/Bacillus-anthracis.html
• http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=191218&lvl=1
• http://www.ncbi.nlm.nih.gov/sites/entrez
• http://www.bt.cdc.gov/agent/anthrax/lab-testing/#references