Unit 4a – Almost done!
Chapter 15: Microbial Mechanisms
of Pathogenicity
• How microbes cause disease (figure 15.9)
Remember?
• Pathogenicity: The ability to cause
disease.
• Virulence: The extent of pathogenicity.
• Most pathogens
have a preferred
portal of entry
• Salmonella typhi
swallowed vs. rubbed
• Strep pneumonia
inhaled vs. swallowed
Numbers of Invading Microbes
• _____: Infectious dose for 50% of a sample population.
• _____: Lethal dose (toxin) for 50% of a sample population.
• actual number depends on:
– virulence of pathogen
– strength of host defenses
• for same pathogen and same person, infective dosage varies from day
to day with strength of body defenses
Clickers…
• What is the LD50 for the bacterial toxin tested in
the experiment below?
• Dilution
mg/kg
a. 6
b. 12.5
c. 25
d. 50
e. 100
# of animals
that died
0
0
3
4
6
# of animals
that survived
6
6
3
2
0
Adherence factors
• for attachment to host cells
attachment by capsule
• Remember Unit 1 discussion of Biofilms?
attachment by filaments
attachment by hook
attachment by viral spikes
Virulence factors: how pathogens
cause disease
• Many pathogens have multiple virulence
factors
• Virulence factors have 5 general effects
– adherence to host cells
– entering into host cells
– destruction of host cells
– avoiding phagocytosis
– evading immune responses
Good Essay Question!
Some exoenzymes of virulence
• 1. collagenase: dissolves collagen (protein fibers
in connective tissue); softens up a tissue so
infection can spread
– Clostridium’s spread of gas gangrene
• 2. IgA proteases
– Destroy our IgA antibodies
– Gonorrhoea and meningococcal meningitis can do
• 3. hyaluronidase: dissolves hyaluronic acid (gluelike substance that holds cells together); helps
infection to spread
– Streptococcus sp.
hyaluronidase dissolving hyaluronic
acid
• 4. lecithinase: dissolves cell membranes;
pathogen can digest cell contents
enzymes of virulence
• 5. coagulases: clot blood; fibrin fibers coat
pathogen, prevent phagocytosis
– Staph (to wall off boils)
• 6. leukocidins: kill white blood cells
– Staph aureus
• 7. kinases: dissolve clots (e.g. streptokinase)
• 8. hemolysins: cause hemolysis (lysis of red
blood cells)
– test for hemolysis on blood agar
– alpha hemolysis: partial hemolysis, causes
greenish zone around colony on blood agar
– beta hemolysis: complete hemolysis, causes
clear, colorless zone around colony
– gamma hemolysis: NO hemolysis
Other virulence factors
• _________: prevents phagocytosis, helps
pathogen attach to host cell
Toxins
•
•
•
•
Toxin: Substances that contribute to pathogenicity.
Toxigenicity: Ability to produce a toxin.
Toxemia: Presence of toxin in the host's blood.
Antitoxin: Antibodies our body produces against a
specific toxin.
• Toxoid: Inactivated toxin used in a vaccine.
– When toxoids are injected as a vaccine, they
stimulate antitoxin production so that immunity is
produced
• Diphtheria and tetanus toxoid vaccination
Exotoxins
• Fig. 15.4
Endotoxins: Fig. 15.4
Endotoxins and the pyrogenic
response
figure 15.6
Sepsis and Septic Shock: pp. 639-641
(10th ed)
•
•
•
Although blood is normally sterile, if the defenses of the cardiovascular and
lymphatic systems fail, microbes could enter blood/lymph
Septicemia: proliferation of pathogens in the blood
– Fever
– Sometimes causes organ damage
Sepsis: systemic inflammatory response syndrome (SIRS)
– Mediators of inflammation into the blood stream
– Fever
– rapid heart or respiratory rates
– High count of white blood cells
– Lymphangitis:
inflamed
lymph vessels
Fig. 23.2 Relationship between the
cardiovascular and lymphatic systems
Sepsis and Septic Shock continued
•
life-threatening systemic response to a bacterial infection
•
First stage is sepsis
– Fever, chills and accelerated breathing & heart rate
•
Overwhelming infection leads to low blood pressure and low blood flow.
– Shock
•
Vital organs, such as the brain, heart, kidneys, and liver may not function
properly or may fail. Decreased urine output from kidney failure may be one
symptom.
– Severe sepsis to septic shock
•
Types
– Gram-Negative Sepsis
• Endotoxic shock
• 750,000 cases/ yr in US; at least 225,000 are fatal (textbook pg.
640)
– Gram-Positive Sepsis
• Staph, Strep & Enterococcus
– Puerperal Sepsis
• Childbirth fever
• Nosocomial infection
• Strep. pyogenes most frequent cause
•
high risk patients:
– Burns
– Age >60 or the very young
– post-surgery (especially intestinal)
– abdominal trauma
– advanced cancer
– diabetes
septic shock
• mechanism: pathogens release endotoxins,
exotoxins:
• these products stimulate release of chemicals
from various host cells that produce the
symptoms:
–
–
–
–
–
low blood pressure, especially when standing
rapid, weak pulse
fever (hypothermia in burn patients)
Low urine output
Agitation, confusion
septic shock
• symptoms:
– sudden high fever
– disorientation, confusion, irritability,
somnolence
– edema (swelling): face, hands, feet
– dyspnea
• edema may constrict pharynx
• bronchioles contract
• death by asphyxiation may result
– circulatory stagnation
• inadequate blood volume causes low blood
pressure, rapid weak pulse, possible total
stagnation of bloodflow
septic shock
• treatment (not necessarily in this order)
–
–
–
–
–
inject epinephrine
open airway (intubation or tracheostomy)
oxygen if needed
restore blood volume: rapid IV
draw blood for blood gases and to culture
pathogen
– broad spectrum drug (until pathogen is known)
– monoclonal antibodies against endotoxin
Back to figure 15.9
In summary: Damage to host cells
• 1. By using the host’s nutrients
– Siderophores: proteins pathogens produce to
get the iron they need from the host
• 2. By causing direct damage in the
immediate vicinity of the invasion
• 3. By producing toxins
Portals of Exit
Respiratory tract
Coughing and sneezing
Gastrointestinal tract
Feces and saliva
Genitourinary tract
Urine and vaginal secretions
Skin
Blood
Biting arthropods and needles
or syringes