Chapter 16

Host Microbe Interactions

Mechanisms of Pathogenesis

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1
A Glimpse of History

 Ancients thought diseases were divine punishment

 Leeuwenhoek’s discovery of microorganisms in 17th century

led people to suspect they might cause disease

 Robert Koch (1876) offered proof of what is now considered

germ theory of disease; showed Bacillus anthracis causes
anthrax
• Formalized criteria for establishing cause of disease,
now known as Koch’s postulates
Koch’s Postulates
Koch's postulates are used to prove the
cause of an infectious disease.
Koch’s Postulates

 Koch's postulates
are used to prove
the cause of an
infectious disease.

• The pathogen
isolated from
inoculated animal is
shown to be the
original pathogen

Figure 14.3
Microbes, Health, and Disease

 Most microbes are harmless

• Many are beneficial
• Normal microbiota (normal flora) are organisms that
routinely reside on body’s surfaces

• Immunocompromised Weaknesses or defects in

innate or adaptive defenses can leave individuals
vulnerable to invasion
– Individuals said to be Factors include malnutrition,
cancer, AIDS or other disease, surgery, wounds,
genetic defects, alcohol or drug abuse, and
immunosuppressive therapy following procedures
such as organ transplants
16.1. The Anatomical Barriers as Ecosystems

 Skin, mucous membranes are barriers

• Also host complex ecosystem of microorganisms
• Example of symbiosis, or “living together”
• Mutualism: both partners benefit
– E.g., in large intestine, some bacteria synthesize
vitamin K and B vitamins, which host can absorb;
bacteria are supplied with warmth, energy sources
• Commensalism: one partner benefits, other is unharmed
– Many microbes living on skin neither harmful nor
helpful, but obtain food and necessities from host
• Parasitism: one organism benefits at expense of other
– All pathogens are parasites, but medical
microbiologists often reserve for eukaryotic
pathogens (e.g., protozoa, helminths)
16.2. The Normal Microbiota
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

 Normal microbiota
• Resident microbiota
inhabit sites for Nose

extended periods Staphylococcus Mouth

Corynebacterium Streptococcus
Fusobacterium

• Transient microbiota Throat

Streptococcus
Actinomyces
Leptotrichia
Moraxella Veillonella
inhabit temporarily Corynebacterium
Haemophilus
Neisseria Skin
• Important to human Mycoplasma Staphylococcus
Propionibacterium

health Largeintestine
Bacteroides

• Relatively little is known Escherichia

Proteus
Klebsiella

• Human Microbiome Lactobacillus

Streptococcus
Candida
Project Clostridium
Pseudomonas
Enterococcus

Urethra Vagina
Streptococcus Lactobacillus
Mycobacterium
Escherichia
Bacteroides
 16.3. Principles of Infectious Disease

 Colonization : microbe establishing itself on body surfaces

• infection can be used to refer to pathogen
• Infectious disease yields noticeable impairment
– Symptoms are subjective effects experienced by patient
(e.g., pain and nausea)
– Signs are objective evidence (e.g., rash, pus formation,
swelling)
• Initial infection is primary infection (ie. Chicken pox)
• Seconday infection Additional infection that occurs as a result
of the primary infection (Chicken pox leading to staph
infections)
– Damage can predispose individual to developing a
secondary infection (e.g., respiratory illness impairing
mucociliary escalator)
16.3. Principles of Infectious Disease

 Pathogenicity
• Primary pathogen is microbe or virus that causes
disease in otherwise healthy individual
• Diseases such as plague, malaria, measles, influenza,
diphtheria, tetanus, tuberculosis, etc.
• Opportunistic pathogen (opportunist) causes disease
only when body’s innate or adaptive defenses are
compromised or when introduced into unusual
location
• Can be members of normal microbiota or common in
environment (e.g., Pseudomonas)
• Virulence refers to degree of pathogenicity
• Virulence factors are traits that allow microorganism
to cause disease
16.3. Principles of Infectious Disease
Stages of Infectious Disease
Incubation Period

depends in virulence of microbe, initial number of microbes,

immune state of patient, generation time, site of infection.
Numbers of Invading Microbes
 ID50: Infectious dose for 50% of the test
population
 LD50: Lethal dose (of a toxin) for 50% of the test
population
 Bacillus anthracis
Portal of Entry ID50
Skin 10–50 endospores

Inhalation 10,000–20,000 endospores

Ingestion 250,000–1,000,000
endospores
16.3. Principles of Infectious Disease

 Duration of Symptoms
• Acute infections: symptoms develop quickly, last a short
time (e.g., strep throat)
• Chronic infections: develop slowly, last for months or
years (e.g., tuberculosis)
• Latent infections: never completely eliminated; microbe
exists in host tissues without causing symptoms
• Chicken pox
• Tuberculosis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

• cold sores Incubation period Illness Convalescence

Acute. Illness is short term because the pathogen is eliminated by the host

• genital herpes defenses; person is usually immune to reinfection.

Incubation period Illness (long lasting)

Chronic. Illness persists over a long time period.

Incubation period Illness Convalescence Latency Recurrence

Latent. Illness may recur if immunity weakens.

16.3. Principles of Infectious Disease

 Distribution of Pathogen
• Localized infection vs Systemic infection
• Bacteremia: bacteria circulating in blood
– Not necessarily a disease state (e.g., can occur
transiently following vigorous tooth brushing

• Viremia: viruses circulating in bloodstream

• Septicemia or sepsis: acute, life-threatening illness
caused by infectious agents or products in bloodstream
• Toxemia: toxins circulating in bloodstream
PATHOGENESIS
 Adherence
 In order for pathogens to establish colonies,
they must adhere to cells
 Adhesins/ligands bind to receptors on host cells
• Glycocalyx: Streptococcus mutans
• Fimbriae: Escherichia coli
• M protein:Streptococcus pyogenes
 Form biofilms
 Colonization
 Siderophores
 IgA proteases
Thought Question:
If a mutation occurred in Escherichia coli that deleted the gene
for a ligand (adhesin), what effect might it have on the ability of
E. coli to cause urinary tract infections?

Figure 15.1
Adherence

Figure 15.1
Q&A

 Almost every
pathogen has a
mechanism for
attaching to host
tissues at their portal
of entry. What is this
attachment called,
and how does it
occur?
Virulence Factors of Infectious
Agents
 Virulence: a measure of pathogenicity (the ability
of an organism to cause disease).

 Beside adhesins, these can be

classified into three categories:
1. Extracellular Enzymes

2. Toxins

3. Anti-phagocytic factors
 Extracellular Enzymes
 These enzymes dissolve structural components/chemicals.
 Examples:
• Hyaluronidase and collagenase: allows bacteria to
invade deeper tissues
 Extracellular Enzymes
 Examples:
• Coagulase: coagulates blood clot proteins, “hiding” the
bacteria
 Extracellular Enzymes
 Examples:
• Kinase: Dissolves clot; releases bacteria from clot

• Ex. Streptokinase,
Staphylokinase
Virulence Factors of Infectious
Agents
 Virulence: a measure of pathogenicity (the
ability of an organism to cause disease).

 Beside adhesins, these can be

classified into three categories:
1. Extracellular Enzymes

2. Toxins

3. Anti-phagocytic factors
Toxins

 Toxin: Substances that contribute to

pathogenicity.
 Toxigenicity: Ability to produce a toxin.
 Toxemia: Presence of toxin in the host's blood.
 Toxoid: Inactivated toxin used in a vaccine.
 Antitoxin: Antibodies against a specific toxin.
Toxins
 Chemicals that harm tissue or elicit host
immune response, damaging tissue.
 Toxemia: toxins enter the bloodstream and
are carried to other parts of the body.
 Two types:
1. Exotoxins
2. Endotoxins
Exotoxins
 Destroy host cells or interfere with host cell
metabolism by secreting toxin from cell
 Three types: cytotoxins, neurotoxins,
enterotoxins

• Examples:
• Clostridium
• Staphylococcus
• E. coli O157:H7
• Algae (dinoflagellates)
THE POWER OF EXOTOXINS

C. TETANUS TOXIN & C. BOTULINUM TOXIN

PER WEIGHT THEY ARE:

 2,000,000 TIMES MORE TOXIC THAN
CYANIDE
 1,300 TIMES MORE TOXIC THAN COBRA
VENOM
Exotoxin

Source Mostly Gram +

Relation to microbe By-products of growing cell
Chemistry Protein
Fever? No
Neutralized by antitoxin? Yes
LD50 Small
Endotoxins
 Gram (-) cell wall have lipopolysaccharides (LPS) on
their outer membrane.
 The lipid part of the LPS is called endotoxin or lipid A.
 Lipid A is released upon bacterial cell death often
causing fever and inflammation.

 At high levels,
endotoxins can
cause hemorrhaging
and septic shock.
Endotoxins

Source Gram
Relation to Microbe Outer membrane
Chemistry Lipid A
Fever? Yes
Neutralized by Antitoxin? No
LD50 Relatively large

Figure 15.4b
Exotoxins and Endotoxins
While does treatment of a Gram (-) infection make
one more sick initially, often seriously?
16.8. Damage to the Host

 Comparison of Exotoxins and Endotoxin

• Exotoxins from Gram-positives and Gram-negatives
• Protein; potent; usually heat-inactivated
• Endotoxins only from Gram-negatives
• Lipid A component of LPS; small localized amounts yield
appropriate response, but systemic distribution can be
deadly; heat-stable
Exotoxins vs Endotoxins
Virulence Factors of Infectious
Agents
 Virulence: a measure of pathogenicity (the
ability of an organism to cause disease).

 Beside adhesins, these can be

classified into three categories:
1. Extracellular Enzymes

2. Toxins

3. Anti-phagocytic factors
Anti-phagocytic factors
 Macrophages (white blood cells) engulf and remove
invading pathogens

5 µm

 Two examples:
• Capsules
• Antiphagocytic chemicals
Capsules

• Made of chemicals normally found in host

• Prevent phagocytosis
 Streptococcus pneumoniae
 Haemophilus influenzae
 Bacillus anthracis
 Anti-phagocytic factors
 Antiphagocytic chemicals:
 Some bacteria secrete chemicals that prevent the fusion of
lysosomes with phagocytic vesicles
 Examples:
 M- protein: protein produced
on its cell wall –resists
phagocytosis
Steptococcus pyogenes
 Opa protein inhibits T helper cells
Neisseria gonorrhoeae
 Leukocidins: kill white blood cells
 Mycolic acid: (waxy lipid) resists digestion Mycobacterium
16.7. Avoiding the Host Defenses

 Avoiding Destruction by Phagocytes

• Preventing Encounters with Phagocytes
• C5a peptidase: degrades chemoattractant C5a
– E.g., Streptococcus pyogenes
• Membrane-damaging toxins: kill phagocytes, other cells
– E.g., S. pyogenes makes streptolysin O
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

1 Prevent encounters
With phagocytes C5a
• C5a peptidase
• Cytolytic toxins

Microbes

2 Avoid recognition
and attachment
• Capsules C3b Phagocyte
• M protein Lysosomes
• Fc receptors

Pseudopod C3b Phagosome

Phagolysosome
C3b receptors
on phagocyte

Digestive
enzymes
3 Survive within phagocytes
• Escape from the phagosome
• Prevent phagosome-
lysosome fusion
• Survive within the phagosome
16.8. Damage to the Host
16.8. Damage to the Host
16.8. Damage to the Host

 Damaging Effects of the Immune Response

• Damage Associated with Inflammation
• Phagocytic cells can release enzymes and toxic products
• Damage Associated with Adaptive Immunity
• Immune complexes: antigen-antibody complexes can
form, settle in kidneys and joints, and activate
complement system leading to inflammation
– E.g., acute glomerulonephritis following skin, throat
infections of S. pyogenes
• Cross-reactive antibodies: may bind to body’s own
tissues, promote autoimmune response
– E.g., acute rheumatic fever following S. pyogenes
infection