BACILLUS ANTHRACIS

Question 1

Major factors responsible for virulence:

Answer 1

◦ Capsule
◦ edema toxin
◦ lethal toxin

Question 2

three toxin protein components

Answer 2

1. Protective antigen (PA)
2. edema factor (EF)
3. lethal factor (LF

Question 3

nontoxic individually but form important toxins when combined ◦ PA plus EF forms________________

◦ PA plus LF forms lethal toxin

Answer 3

edema toxin

forms lethal toxin

Question 4

–83-kDa protein that is –most immunogenic of the B. anthracis
—

Answer 4

◦Protective antigen (PA)

Question 5

◦zinc-dependent protease
◦Capable of cleaving mitogen-activated protein (MAP) kinase
◦leads to cell death by incompletely understood mechanisms

◦zinc metalloprotease activity of lethal toxin stimulates macrophages to release tumor necrosis factor-α (TNF- α), interleukin-1β (IL-1β), and other proinflammatory cytokines
◦mediates lysis of macrophages in selected cell cultures
◦

Answer 5

—Lethal Factor

Question 6

◦calmodulin-dependent adenylate cyclase
◦increases the intracellular cyclic adenosine monophosphate (cAMP) levels, resulting in edema
◦adenylate cyclase activity responsible for fluid accumulation
◦related to the adenylate cyclases produced by Bordetella pertussis and Pseudomonas aeruginosa
—

Answer 6

—Edema Factor

Question 7

◦inhibits phagocytosis of replicating cells
◦Consists of poly-D-glutamic acid
◦observed in clinical specimens but is not produced in vitro unless special growth conditions are used

Answer 7

—Polypeptide Capsule

Question 8

◦3 genes responsible for synthesis of capsule
◦

Answer 8

capA, capB, and capC

Question 9

PA Bond to receptors of many cells in tissues(e.g., brain, heart, intestine, lung, skeletal muscle, pancreas, macrophages)

host proteases cleave PA

—

Releases a small fragment and retaining the 63-kDa fragment (PA63) on the cell surface

◦PA63 fragments self-associate on the cell surface
—
◦formis a ring-shaped complex of seven fragments (pore precursor or “prepore”) which can bind up to three molecules of LF and/or EF (competitive binding)
—
◦complex stimulates endocytosis and movement to an acidic compartment

—
—
–heptameric complex forms a transmembrane pore and releases LF and EF into the cell cytosol
–

Cell Death

—

Question 10

—primarily a disease of herbivores
—Humans infected through exposure to contaminated animals or animal products
—serious problem in countries where animal vaccination is not practiced or is impractical
—Rarely seen in the United States
◦five cases reported between 1981 and 1999
—Used for bioterrorism
◦deliberate contamination of the U.S. Postal Service with B. anthracis spores in 2001

Answer 10

B. anthracis

Question 11

—Human B. anthracis disease acquired by the following three routes:

—

Answer 11

◦Inoculation
◦Ingestion
◦Inhalation
◦

Question 12

◦95% of infections result from the_________of Bacillus sporesthrough exposed skin:
◦contaminated soil
◦infected animal products
–hides,
–Goat hair
–wool

Answer 12

—Inoculation

Question 13

◦common route of infection in herbivores
◦very rare in humans
◦contaminated soil or animal products can remain infectious for many years
◦Due to formation of resilient spores

Answer 13

—Ingestion

Question 14

◦uncommon source for human infections
◦Most likely route of infection with biologic weapons
◦wool-sorters’ disease
◦during the processing of goat hair
◦infectious dose of the organism is believed to be low
◦Person-to-person transmission does not occur

Answer 14

—Inhalation

Question 15

–bacterial replication occurs in the______________rather than the bronchopulmonary tree
◦

Answer 15

mediastinal lymph nodes

Question 16

◦starts with the development of a painless papule at the site of inoculation
◦rapidly progresses to an ulcer surrounded by vesicles

—rapidly progresses to an ulcer surrounded by vesicles then to a necrotic eschar
—Systemic signs, painful lymphadenopathy, and massive edema may develop
—mortality rate in untreated patients
◦20%

2 to 5 days incubation pd

Answer 16

—Cutaneous Anthrax

Question 17

◦determined by the site of the infection
◦mortality believed to approach 100%
◦upper intestinal tract
–ulcers form in the mouth or esophagus
–Leads to regional lymphadenopathy, edema, and sepsis

◦cecum or terminal ileum
–Presents with nausea, vomiting, and malaise
–rapidly progress to systemic disease

Answer 17

—Gastrointestinal Anthrax

Question 18

◦associated with a prolonged latent period
–2 months or more

–Asymptomatic
◦can remain latent in the nasal passages or reach the lower airways
◦Alveolar macrophages ingest the inhaled spores and transport them to the mediastinal lymph nodes
—

Answer 18

—Inhalation anthrax

Question 19

What is the initial symptom of B. anthracis

Answer 19

—initial clinical symptoms of disease are nonspecific
◦fever
◦Myalgias
◦nonproductive cough
◦Malaise
◦
—

Question 20

—Striking second stage of disease

Answer 20

◦pneumonia rarely develops
◦Rapidly worsening course
◦fever
◦Edema
◦Meningeal symptoms (50%)
◦ massive enlargement of the mediastinal lymph nodes
–responsible for the widened mediastinum observed on chest radiography
◦Respiratory failure
◦Sepsis
◦Almost all cases progress to shock and death within 3 days of initial symptoms
◦

Question 21

—Serologic evidence indicates that a subclinical or asymptomatic form of inhalation anthrax does not exist
—
—Virtually all patients who develop disease progress to a fatal outcome unless prompt medical intervention started

Question 22

—Infections characterized by overwhelming numbers of organisms present
◦wounds
◦Involved lymph nodes
◦blood
—organisms can be seen when peripheral blood is Gram stained

Question 23

—diagnostic difficulty in distinguishing B. anthracis from other members of the taxonomically related B. cereus group
—
—Preliminary identification of B. anthracis based on___________________

Answer 23

microscopic and colonial morphology
—

Question 24

How is B.anthracis arranged?

Answer 24

—arranged as single or paired rods or as long, serpentine chains
—

Question 25

—Spores are not observed in clinical specimens **◦only in culture**s incubated in a** low carbon dioxide (CO2)** atmosphere ◦**best seen with the use of a special spore stain** \_\_\_\_\_\_\_\_\_\_\_\_\_\_ —

Answer 25

–i.e. malachite green stain

Question 26

—capsule produced in vivo but **not typically observed in culture** * *—can be observed with a contrasting stain** * *\_\_\_\_\_\_\_\_\_\_\_\_\_**

Answer 26

**◦india ink** ◦ M’Fadyean methylene blue stain ◦direct fluorescent ◦antibody (DFA)

Question 27

n contrast with B. cereus the colonies of B. anthracis are —

Answer 27

—Colonies not hemolytic

Question 28

—B. anthracis will appear\_\_\_\_\_\_\_\_\_\_\_\_- in motility tests, such as the microscopic observation of individual rods in a suspended drop of culture medium —

Answer 28

nonmotile

Question 29

**—definitive identification of nonmotile, nonhemolytic organisms** resembling B. anthracis made in a \_\_\_\_\_\_\_\_\_\_\_\_\_ —

Answer 29

public health reference laboratory —

Question 30

—accomplished by _________________ (by microscopy or DFA) and **either lysis of the bacteria with gamma phage or a positive** DFA test for a specific B. anthracis cell wall polysaccharide — — —

Answer 30

demonstrating capsule production

Question 31

\_\_\_\_\_\_\_\_\_\_\_\_\_\_ the traditional drug of choice —Resistance in naturally occurring strains has been observed —current empiric treatment recommendation —

Answer 31

—penicillin

Question 32

**◦ciprofloxacin or doxycycline** combined with one or two additional antibiotics (**e.g., rifampin, vancomycin, penicillin, imipenem, clindamycin, clarithromycin) ◦**

Question 33

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_) still recommended for naturally acquired cutaneous anthrax

Answer 33

◦oral penicillin (amoxicillin

Question 34

How is preventon achieved?

Answer 34

—Control of naturally acquired human disease **◦vaccination of animal herds in endemic regions** ◦Vaccination used to protect: –People who live in areas where the disease is endemic –people who work with animal products imported from –countries with endemic anthrax –military personnel