Chapter 11: Bacillus and Clostridium Species
I. Bacillus Species
A. General Characteristics
•
Gram-positive, spore-forming bacilli.
•
Found ubiquitously in nature (soil, water, air, and
vegetation).
•
They survive extreme conditions due to spore
formation.
•
Bacillus species include both non-pathogenic
saprophytic organisms and highly virulent species.
•
Major pathogenic species:
1. Bacillus anthracis (anthrax)
2. Bacillus cereus (food poisoning and
infections)
B. Bacillus anthracis (Anthrax)
1.
2.
3.
4.
Morphology and Identification
o Size: Large bacilli, 1 × 3–4 µm.
o Shape: Square ends, arranged in chains, with
centrally located spores.
o Capsule: Virulent strains produce a poly-γ-dglutamic acid capsule (antiphagocytic).
Culture Characteristics
o Colonies: Round, gray-white colonies with a
“cut glass” appearance.
o Hemolysis: Non-hemolytic on blood agar.
o Motility: Non-motile (distinguishing feature
from B. cereus).
Pathogenesis and Virulence Factors
o Anthrax Toxins:
▪
Protective Antigen (PA): Binds to
receptors and forms a channel for
toxin entry.
▪
Edema Factor (EF): Adenylate
cyclase that increases cyclic AMP,
causing edema.
▪
Lethal Factor (LF): Protease that
disrupts immune response, leading
to cell death.
o Pathogenesis: Anthrax spores enter through
the skin, mucosa, or lungs. Germination
occurs, leading to local edema, followed by
systemic spread and sepsis.
Clinical Manifestations
o Cutaneous Anthrax (95%): Begins as a
papule, then forms a necrotic ulcer with a
black eschar. Can cause sepsis if untreated.
o Inhalational Anthrax: Flu-like symptoms,
hemorrhagic mediastinitis, and septic shock.
o Gastrointestinal Anthrax: Caused by
ingestion of spores; severe abdominal pain,
vomiting, bloody diarrhea.
Injection Anthrax: Related to heroin users;
characterized by extensive edema and
septicemia.
Laboratory Diagnosis
o Microscopy: Large Gram-positive rods in
chains.
o Culture: Growth on blood agar with
characteristic colonies.
o Confirmation: PCR for toxin genes,
immunofluorescence,
or
specific
bacteriophage lysis.
Treatment
o First-line
antibiotics:
Ciprofloxacin,
doxycycline, or penicillin.
o For bioterrorism exposure: Ciprofloxacin or
doxycycline for 60 days plus anthrax vaccine.
o Antitoxins: Raxibacumab or Anthrax
Immune Globulin (AIGIV) to neutralize toxins.
Prevention
o Vaccination: AVA BioThrax® for military
personnel or high-risk individuals.
o Control: Proper disposal of infected animal
carcasses, use of protective clothing.
o
5.
6.
7.
C. Bacillus cereus
1.
2.
3.
4.
5.
Overview
o A common soil bacterium causing food
poisoning and occasional infections in
immunocompromised individuals.
Food Poisoning
o Emetic Form:
▪
Associated with improperly stored
rice.
▪
Toxin causes nausea and vomiting
1–5 hours after ingestion.
o Diarrheal Form:
▪
Associated with contaminated meat
or vegetables.
▪
Toxin causes watery diarrhea and
abdominal pain 8–16 hours after
ingestion.
Infections
o Causes severe ocular infections, including
endophthalmitis and keratitis.
o Can cause systemic infections (meningitis,
endocarditis, and bacteremia), particularly in
immunocompromised patients.
Diagnosis
o Culture: Grows on blood agar with βhemolysis.
o Microscopy: Gram-positive, motile rods.
o Food poisoning diagnosis: Based on history
of food consumption and toxin assays in food
or stool.
Treatment
o
o
For food poisoning, treatment is supportive.
Serious
infections:
Vancomycin,
clindamycin, or ciprofloxacin.
2.
II. Clostridium Species
A. General Characteristics
•
Gram-positive, spore-forming bacilli.
•
Obligate anaerobes.
•
Commonly found in soil, marine sediments, sewage,
and intestines of animals.
•
Highly virulent due to toxin production, causing
diseases like tetanus, botulism, gas gangrene, and
pseudomembranous colitis.
B. Clostridium tetani (Tetanus)
1.
2.
3.
4.
5.
6.
7.
Morphology and Identification
o Gram-positive, motile rods with terminal
spores (drumstick appearance).
o Anaerobic growth.
Toxin
o Tetanospasmin: Neurotoxin that blocks
release of inhibitory neurotransmitters (GABA,
glycine), causing spastic paralysis.
Pathogenesis
o Spores enter through a wound and germinate
in anaerobic conditions.
o Toxin travels to the CNS, blocking inhibitory
signals, leading to muscle spasms.
Clinical Manifestations
o Lockjaw (trismus), followed by muscle
stiffness and spasms.
o Generalized tetanus leads to severe muscle
spasms and respiratory failure.
Diagnosis
o Based on clinical presentation and history of
injury.
o Isolation of C. tetani is not required for
diagnosis.
Treatment
o Tetanus immune globulin (TIG) to neutralize
unbound toxin.
o Antibiotics: Penicillin or metronidazole.
o Supportive
care:
Muscle
relaxants,
mechanical ventilation if necessary.
Prevention
o Vaccination with tetanus toxoid (part of DPT
vaccine).
o Booster doses every 10 years.
3.
4.
5.
6.
7.
D. Clostridium perfringens
1.
2.
3.
4.
C. Clostridium botulinum (Botulism)
1.
Morphology and Identification
Gram-positive rods, anaerobic, sporeforming.
o Toxin-producing strains differentiated by toxin
types (A-G).
Botulinum Toxin
o One of the most potent neurotoxins, blocks
acetylcholine release at neuromuscular
junctions, causing flaccid paralysis.
Types of Botulism
o Foodborne botulism: Ingestion of preformed
toxin in improperly preserved food (canned,
smoked, vacuum-packed).
o Infant botulism: Ingestion of spores, often
from honey, leading to toxin production in the
gut.
o Wound botulism: Contamination of wounds
with spores, often seen in injection drug users.
Clinical Manifestations
o Symptoms begin 18–24 hours after toxin
ingestion:
double
vision,
difficulty
swallowing, descending flaccid paralysis.
o In infant botulism, signs include poor feeding
and floppy baby syndrome.
Diagnosis
o Detection of toxin in serum, stool, or food
via mouse bioassay or ELISA.
o Culture of C. botulinum from clinical samples.
Treatment
o Antitoxin administration as soon as possible
to neutralize circulating toxin.
o Supportive care, including respiratory
support (mechanical ventilation).
Prevention
o Proper food handling: Boil food for 20
minutes before consumption.
o Avoid honey in infants under 1 year.
o
Gas Gangrene (Clostridial Myonecrosis)
o C. perfringens is the most common cause of
gas gangrene, characterized by rapid tissue
destruction and gas formation.
Pathogenesis
o Spores enter through traumatic wounds.
o Alpha toxin (lecithinase) destroys cell
membranes, causing tissue necrosis.
o Gas formation due to carbohydrate
fermentation.
Clinical Presentation
o Severe pain, swelling, and crepitus in tissues.
o Rapid progression to sepsis and shock.
Diagnosis
o Microscopy: Large Gram-positive rods.
o Culture: Anaerobic growth with double zone
hemolysis.
5.
6.
Treatment
o Surgical debridement is essential.
o High-dose penicillin.
o Hyperbaric oxygen therapy may be used to
inhibit bacterial growth.
Food Poisoning
o Caused by enterotoxin-producing strains.
o Symptoms: Diarrhea and abdominal cramps
within 6–24 hours of ingestion.
o Self-limiting, no specific treatment required.
E. Clostridium difficile
1.
2.
3.
4.
Pseudomembranous Colitis
o Caused by overgrowth of C. difficile after
antibiotic use.
o Produces Toxin A (enterotoxin) and Toxin B
(cytotoxin), leading to colonic inflammation
and diarrhea.
Clinical Manifestations
o Watery diarrhea, fever, abdominal pain, and
pseudomembranes in the colon.
Diagnosis
o Toxin detection in stool via ELISA or PCR.
o Endoscopic findings: Pseudomembranes in
the colon.
Treatment
o Discontinuation of the causative antibiotic.
o First-line treatment: Metronidazole or
vancomycin.
o For recurrent infections: Fecal microbiota
transplantation.
Clinical Cases in Spore-Forming Gram-Positive Bacilli
Case 1: Botulism
A 35-year-old housewife living on a farm presents to the
emergency department with the following symptoms:
•
Chief Complaints: Double vision and difficulty talking.
•
History: Symptoms began 2 hours ago, and she
noticed a dry mouth and generalized weakness. The
night before, she served home-canned green beans,
which she tasted before boiling. None of the other
family members are ill.
Key Clinical Signs:
•
Neurological: Symmetrical descending paralysis
affecting cranial nerves, upper extremities, and trunk.
Diagnosis:
•
Botulism caused by ingestion of botulinum toxin in
improperly canned food.
Management:
•
Treatment: Immediate administration of botulinum
antitoxin and supportive care, including mechanical
ventilation if necessary.
Learning Points:
•
Botulism presents as descending flaccid paralysis
due to inhibition of acetylcholine release by the
botulinum toxin.
•
Foodborne botulism is associated with improperly
canned or preserved foods that allow spores of C.
botulinum to germinate and produce toxins.
Case 2: Gas Gangrene (Clostridium perfringens)
III. Key Concepts Summary
•
•
•
•
Bacillus species are aerobic, spore-forming bacteria,
with Bacillus anthracis causing anthrax and Bacillus
cereus causing food poisoning.
Clostridium species are anaerobic, spore-forming
bacteria that cause diseases through potent exotoxins,
including C. tetani (tetanus), C. botulinum (botulism),
C. perfringens (gas gangrene), and C. difficile
(pseudomembranous colitis).
Diagnosis often involves identifying the organism in
clinical specimens or detecting toxins.
Prevention includes vaccination (e.g., tetanus), proper
food handling (botulism), and careful antibiotic use (C.
difficile).
A young man sustains major soft tissue injury and open fractures
of his right leg in a motorcycle accident. One day later, he
develops the following symptoms:
•
Chief Complaints: Fever (38°C), increased heart rate,
sweating, and restlessness.
•
Physical Examination: The leg is swollen and tense,
with dark serous fluid draining from the wounds. The
skin is cool, pale, and shiny. Crepitus is present
(indicating gas formation in tissues).
Key Clinical Signs:
•
Hematocrit is 20% (50% of normal), and circulating
hemoglobin is normal. Serum shows free hemoglobin.
Diagnosis:
•
Gas gangrene caused by Clostridium perfringens,
based on clinical presentation and crepitus (gas
formation) in the tissues.
Hemolysis:
•
Hemolysis in this patient is likely due to the action of
lecithinase (alpha toxin) produced by C. perfringens,
which lyses cell membranes and causes tissue
necrosis.
Management:
•
Emergency surgical debridement to remove necrotic
tissue.
•
High-dose penicillin and possibly hyperbaric oxygen
therapy to inhibit bacterial growth.
Learning Points:
•
Gas gangrene is a rapidly progressing, life-threatening
infection characterized by myonecrosis and gas
production. Early surgical intervention is essential to
prevent further tissue destruction and systemic sepsis.
Management:
•
Treatment: Supportive care for symptoms, which
typically resolve within 24 hours.
Learning Points:
•
B. cereus food poisoning has two distinct forms:
emetic (associated with fried rice) and diarrheal
(associated with contaminated meat dishes). The
emetic form is caused by a heat-stable toxin that
induces rapid-onset vomiting.
Case 5: Tetanus (Clostridium tetani)
Case 3: Anthrax
A bioterrorism event results in 22 cases of anthrax, 11 of which
are inhalational and 11 are cutaneous. Among the inhalational
cases, five patients die. Symptoms in these patients included:
•
Chief Complaints: Flu-like symptoms initially, followed
by substernal chest pain, cough, and difficulty
breathing.
•
Physical Examination:
Hemorrhagic pleural
effusions, pronounced mediastinal widening (visible
on chest X-rays), and rapidly progressing sepsis.
Diagnosis:
•
Inhalational anthrax, caused by inhalation of Bacillus
anthracis spores, based on clinical presentation and
history of bioterrorism exposure.
Pathogenesis:
•
Lethal toxin (LF) and edema toxin (EF), combined
with protective antigen (PA), cause extensive
hemorrhagic mediastinitis and sepsis, which are
often fatal.
Management:
•
Early antibiotic treatment with ciprofloxacin or
doxycycline.
•
Post-exposure prophylaxis for those at risk, including
60 days of antibiotic therapy and three doses of anthrax
vaccine.
Learning Points:
•
Inhalational anthrax is rare but highly fatal, especially
if diagnosis and treatment are delayed. Rapid
progression to sepsis and hemorrhagic mediastinitis
are hallmark features.
A 45-year-old man who immigrated to the U.S. 5 years ago
presents with muscle spasms, particularly in his right leg,
following a puncture wound from a lawn mower injury.
Symptoms progressed over several days, and by day 8, he was
unable to open his jaw (lockjaw).
Key Clinical Signs:
•
Generalized muscle spasms triggered by stimuli (e.g.,
loud noises).
Diagnosis:
•
Tetanus, caused by C. tetani, based on clinical
presentation and recent puncture wound.
Pathogenesis:
•
The tetanospasmin toxin produced by C. tetani blocks
release of inhibitory neurotransmitters (GABA and
glycine), leading to spastic paralysis.
Management:
•
Tetanus immune globulin (TIG) to neutralize unbound
toxin.
•
Antibiotics (penicillin or metronidazole) to clear the
infection.
•
Supportive care: Sedation and muscle relaxants, and
possible mechanical ventilation.
Learning Points:
•
Tetanus presents with muscle stiffness, lockjaw, and
generalized spasms. Tetanospasmin blocks inhibitory
neurotransmitter release, resulting in uncontrolled
muscle contractions.
Review Questions from Clinical Cases
5.
Case 4: Food Poisoning (Bacillus cereus)
A food commonly associated with Bacillus cereus food
poisoning is fried rice. The patient, a 30-year-old woman,
presents with the following symptoms after consuming fried rice
at a restaurant:
•
Chief Complaints: Nausea, vomiting, and abdominal
cramps that began 2 hours after eating.
Diagnosis:
•
Bacillus cereus food poisoning, emetic form, based
on the short incubation period (1–5 hours) and
ingestion of improperly stored fried rice.
6.
7.
Botulism Case: What is the most likely cause of the
symmetrical descending paralysis?
o Answer: Botulism (caused by ingestion of
botulinum toxin).
Gas Gangrene Case: Which microorganism is
responsible for the hemolysis and gas production in the
wound?
o Answer: Clostridium perfringens, producing
alpha toxin (lecithinase).
Anthrax Case: What is the recommended postexposure prophylaxis for inhalational anthrax in a
bioterrorism event?
Answer: Ciprofloxacin or doxycycline for 60
days, plus vaccination.
Bacillus cereus Case: What food is most commonly
associated with the emetic form of Bacillus cereus food
poisoning?
o Answer: Fried rice.
Tetanus Case: What neurotransmitters are blocked by
tetanus toxin, leading to spastic paralysis?
o Answer: Glycine and γ-aminobutyric acid
(GABA).
o
8.
9.
Flashcards
Bacillus Species: General Characteristics
Flashcard 1
Q: What are the general characteristics of Bacillus species?
A: Bacillus species are large, Gram-positive, spore-forming rods
that are aerobic or facultatively anaerobic, commonly found in
soil, water, and vegetation.
Flashcard 2
Q: Name the two most clinically significant Bacillus species.
A: Bacillus anthracis (causes anthrax) and Bacillus cereus
(causes food poisoning and infections).
Bacillus anthracis: Morphology and Identification
Flashcard 3
Q: Describe the morphology of Bacillus anthracis.
A: Bacillus anthracis is a large, Gram-positive bacillus with
square ends, arranged in chains, and forms central spores.
Virulent strains are encapsulated with a poly-γ-d-glutamic acid
capsule.
Flashcard 4
Q: What is the appearance of Bacillus anthracis colonies on
blood agar?
A: Non-hemolytic, gray-white colonies with a “ground-glass”
appearance.
Flashcard 5
Q: Is Bacillus anthracis motile?
A: No, Bacillus anthracis is non-motile, which helps differentiate
it from Bacillus cereus.
Bacillus anthracis: Pathogenesis and Virulence Factors
Flashcard 6
Q: What are the three main components of the anthrax toxin?
A: Protective Antigen (PA), Edema Factor (EF), and Lethal
Factor (LF).
Flashcard 7
Q: How does Protective Antigen (PA) function in anthrax
pathogenesis?
A: PA binds to host cell receptors and forms a channel through
which Edema Factor (EF) and Lethal Factor (LF) enter the cell.
Flashcard 8
Q: What does Edema Factor (EF) do in anthrax infections?
A: EF is an adenylate cyclase that increases cyclic AMP, causing
cell edema and fluid accumulation.
Flashcard 9
Q: What role does Lethal Factor (LF) play in anthrax?
A: LF is a protease that disrupts immune cell signaling, leading
to cell death and contributing to systemic shock and death.
Bacillus anthracis: Clinical Manifestations
Flashcard 10
Q: What are the four types of anthrax in humans?
A: Cutaneous anthrax, inhalational anthrax, gastrointestinal
anthrax, and injection anthrax.
Flashcard 11
Q: What is the most common form of anthrax, and what are its
symptoms?
A: Cutaneous anthrax (95% of cases) begins as a pruritic
papule, progresses to a vesicle, and forms a black eschar
surrounded by edema. Without treatment, it can lead to sepsis.
Flashcard 12
Q: Describe the progression of inhalational anthrax.
A: Inhalational anthrax starts with flu-like symptoms, then
progresses to hemorrhagic mediastinitis, pleural effusion, and
sepsis, leading to rapid death.
Flashcard 13
Q: What is gastrointestinal anthrax?
A: Gastrointestinal anthrax occurs after ingestion of spores,
leading to severe abdominal pain, vomiting, bloody diarrhea, and
possible sepsis.
Flashcard 14
Q: What is injection anthrax, and who is at risk?
A: Injection anthrax occurs in drug users who inject
contaminated heroin. It causes painless, extensive
subcutaneous edema, progressing to septicemia.
Bacillus anthracis: Diagnosis and Treatment
Flashcard 15
Q: How is anthrax diagnosed in the lab?
A: Diagnosis is based on Gram-stained smears (showing large
Gram-positive rods in chains), culture on blood agar (nonhemolytic, ground-glass colonies), and PCR for toxin genes.
Flashcard 16
Q: What are the first-line antibiotics for treating anthrax?
A: Ciprofloxacin or doxycycline, usually combined with
additional antibiotics for severe cases.
Flashcard 17
Q: What antitoxins are used in the treatment of anthrax?
A: Raxibacumab (a monoclonal antibody) and Anthrax
Immune Globulin (AIGIV), which neutralize anthrax toxins.
Flashcard 18
Q: What is the anthrax vaccine, and who should receive it?
A: The anthrax vaccine (AVA BioThrax®) is given to military
personnel, lab workers, and others at high risk of exposure to
Bacillus anthracis.
Flashcard 27
Q: What are the four major diseases caused by Clostridium
species?
A: Tetanus, botulism, gas gangrene, and pseudomembranous
colitis.
Bacillus cereus: Pathogenesis and Clinical Manifestations
Flashcard 19
Q: What are the two types of food poisoning caused by Bacillus
cereus?
A: Emetic type (vomiting) and diarrheal type.
Clostridium tetani: Pathogenesis and Clinical Manifestations
Flashcard 28
Q: What is the primary toxin produced by Clostridium tetani, and
what is its effect?
A: Tetanospasmin, a neurotoxin that blocks the release of
inhibitory neurotransmitters (GABA and glycine), causing
spastic paralysis.
Flashcard 20
Q: What foods are commonly associated with the emetic form of
Bacillus cereus food poisoning?
A: Fried rice that has been improperly stored.
Flashcard 29
Q: How do Clostridium tetani spores enter the body?
A: Through a puncture wound or trauma, especially in areas with
low oxygen tension.
Flashcard 21
Q: What are the symptoms of the emetic form of Bacillus cereus
food poisoning?
A: Nausea and vomiting within 1–5 hours after consuming the
contaminated food.
Flashcard 30
Q: What are the key symptoms of tetanus?
A: Muscle stiffness, lockjaw (trismus), generalized muscle
spasms, and respiratory failure.
Flashcard 22
Q: What foods are commonly associated with the diarrheal form
of Bacillus cereus food poisoning?
A: Meat dishes, sauces, and vegetables.
Flashcard 23
Q: What are the symptoms of the diarrheal form of Bacillus
cereus food poisoning?
A: Profuse diarrhea, abdominal pain, and cramps occurring 8–
16 hours after ingestion.
Bacillus cereus: Infections and Treatment
Flashcard 24
Q: Apart from food poisoning, what other infections can Bacillus
cereus cause?
A: Severe eye infections (keratitis, endophthalmitis), wound
infections, meningitis, and catheter-associated bacteremia.
Flashcard 25
Q: What is the treatment for serious Bacillus cereus infections?
A: Vancomycin, clindamycin, or ciprofloxacin for systemic
infections. For food poisoning, supportive care is typically
sufficient.
Clostridium Species: General Characteristics
Flashcard 26
Q: What are the general characteristics of Clostridium species?
A: Clostridium species are large, Gram-positive, spore-forming
bacilli that are obligate anaerobes and produce a variety of
toxins. They are found in soil, marine sediments, sewage, and
the intestines of animals and humans.
Clostridium tetani: Diagnosis and Treatment
Flashcard 31
Q: How is tetanus diagnosed?
A: Tetanus is diagnosed based on clinical presentation and
history of a wound. Laboratory confirmation is not necessary.
Flashcard 32
Q: What is the treatment for tetanus?
A: Tetanus immune globulin (TIG) to neutralize toxin,
antibiotics (penicillin or metronidazole), wound debridement,
and supportive care such as muscle relaxants and mechanical
ventilation if necessary.