TORTORA FUNKE

CASE

Microbiology
AN INTRODUCTION
EIGHTH EDITION

B.E Pruitt & Jane J. Stein

Chapter 15
Microbial Mechanisms of Pathogenicity

Microbial Mechanisms of
Pathogenicity
Pathogenicity
The ability to cause disease
Virulence
The extent of pathogenicity
Many properties that determine a microbes pathogenicity or
virulence are unclear or unknown
But, when a microbe overpowers the hosts defenses,
disease results!

They need to gain entry, adhere, penetrate and

cause damage to cause disease.

Disease: Pathogens may cause damage to host

Direct damage in the immediate vicinity

Far removed from site of invasion by toxins

Grow and multiply and clog cells and passageways

Toxins spread through blood and lymph

By hypersensitivity

The hosts reaction may cause the damage

Portals of Entry
Entry of a Microbe
Need to adhere, penetrate, and then cause damage
Gain access via portal of entry and may a have preferred portal
of entry - Streptococcus pneumoniae via GI tract? Small pox via
vein?
Portals of Entry:
Mucous membranes
Respiratory
GI
Urogenital
conjunctiva

Skin
Tough so rare - Necator americanus - hookworm

Parenteral route
Puncture or injection

Mucous Membranes: Respiratory

Respiratory Tract
microbes inhaled
into mouth or
nose in droplets
of moisture or
dust particles
Easiest and most
frequently
traveled portal of
entry

Common cold
Flu
Tuberculosis
Whooping cough
Pneumonia
Measles
Strep Throat
Diphtheria

Mucous membranes: G.I. Tract

Salmonellosis
Salmonella sp.
Shigellosis
Shigella sp.
Cholera
Vibrio cholorea
Ulcers

Fecal - Oral Diseases

Helicobacter pylori These pathogens enter the G.I.

Tract at one end and exit at the
Botulism
Clostridium
botulinum

other end.
Spread by contaminated hands &
fingers or contaminated food &
water
Poor personal hygiene.

Mucous Membranes of the Genitourinary System - STDs

Gonorrhea
Neisseria gonorrhoeae
Syphilis
Treponema pallidum
Chlamydia
Chlamydia trachomatis
HIV
Herpes Simplex II

Mucous Membranes: Conjunctiva

Conjunctiva

mucous membranes that cover the

eyeball and lines the eyelid

Trachoma
Chlamydia trachomatis

2nd Portal of Entry: Skin

Skin - the largest organ of the body. When unbroken is

an effective barrier for most microorganisms.
Some microbes can gain entrance thru openings in the
skin: hair follicles and sweat glands

3rd Portal of Entry: Parenteral

Microorganisms are deposited into the tissues below the

skin or mucous membranes
Punctures
injections
bites
scratches
surgery
splitting of skin due to swelling or dryness

Preferred Portal of Entry

Just because a pathogen enters your body it does not
mean its going to cause disease.
pathogens - preferred portal of entry
Small pox via variolation
Streptococcus pneumoniae
if inhaled can cause pneumonia
if enters the G.I. Tract, no disease
Salmonella typhi
if enters the G.I. Tract can cause Typhoid Fever
if on skin, no disease

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
Example: ID50 for Vibrio cholerea 108 cells
(100,000,000 cells)
ID50 for Inhalation Anthrax - 5,000 to 10,000 spores ????

ID50 and LD50 for Bacillus anthracis

Portal of entry

ID50

Skin

??? endospores

Inhalation

10,000-20,000 endospores

Ingestion

250,000-1,000,000 endospores

Key traits to a pathogen

The ability to:
1. Adherence
To host surfaces and not be washed off
2. Avoid phagocytosis
Prevent host defenses from destroying
3. Penetrate
Get into host and spread
4. Produce Enzymes
Spread, prevent host defenses and
cause damage at or near site of
infection
5. Produce Toxins
Cause damage at distant site

Adherence

Adhesions/ligands bind to receptors on host cells

so wont get flushed off.
Mechanisms to adhere and avoid host defenses:
Glycocalyx Streptococcus mutans
Dextran (plaque)

Waxes

Mycobacteria

Fimbriae

Escherichia coli

M protein

Streptococcus pyogenes

Tapered end w/ hooks Treponema pallidum

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Capsules
Prevent phagocytosis
and help with attachment
(adherence)
Streptococcus pneumoniae
Klebsiella pneumoniae
Haemophilus influenzae
Bacillus anthracis
Streptococcus mutans
Yersinia pestis

Enzymes to help penetration

Many pathogens secrete enzymes that contribute to their
pathogenicity:
Increase virulence by use of enzymes
And avoid phagocytosis
Coagulase
make boil

Coagulate blood - wall off from host

Kinases
spreading

Digest fibrin clot - allow

streptokinase and staphylolinase

Hyaluronidase
Hydrolyses hyaluronic
acid connective tissue
Collagenase

Hydrolyzes collagen

IgA proteases

Destroy IgA antibodies

Hemolysins

lyse RBCs

Hemolysins
Alpha Hemolytic Streptococci
- secrete hemolysins that cause the incomplete
lysis or RBCs

Beta Hemolytic Streptococci

- secrete hemolysins that cause the complete lysis of
RBCs

Leukocidins

Enzymes that attack certain types of WBCs

1. Kills WBCs which prevents phagocytosis
2. Releases & ruptures lysosomes
lysosomes - contain powerful hydrolytic enzymes
which then cause more tissue damage

Enzymes: Necrotizing Factor

Flesh Eating Bacteria
Necrotizing fasciitis
causes death (necrosis) to tissue cells

Summary of How Bacterial Pathogens Penetrate Host Defenses

1. Adherence
2. Capsule

3. Enzymes
leukocidins
Hemolysins
Coagulase
Kinases
Hyaluronidase
Collagenase
Necrotizing Factor

Penetration into the Host Cell

Figure 15.2

Toxins
Provide properties to spread and cause damage to the host.
Compare endotoxins and exotoxins
Endotoxins from inside the cell. Released upon cell lysis.
Exotoxins are secreted out of the cell during cell life.
Toxin
Substances that contribute to
pathogenicity
Toxigenicity Ability to produce a toxin
Toxemia
Presence of toxin the host's blood
Toxoid
Inactivated toxin used in a vaccine
Antitoxin
Antibodies against a specific toxin

Exotoxins
Mostly seen in Gram (+)
Bacteria
Most gene that code for
exotoxins are located on
plasmids or phages

Figure 15.4a

Exotoxin
Exotoxin

Source
Metabolic product
Chemistry

Mostly Gram +
By-products of growing cell
Protein
Water soluble

Fever?

No

Neutralized by antitoxin

Yes

LD50

Small - Very potent

1 mg of Clostridium botulinum toxin
can kill 1 million guinea pigs

Exotoxins - three types

1. Cytotoxins
kill cells
2. Neurotoxins
interfere with normal nerve
impulses
3. Enterotoxins
effect cells lining the G.I.
Tract
Many toxins have A-B subunit toxins
or type III toxins
A - active
Causes change in
host
B - binding

Figure 15.5

Exotoxins
OR

Superantigens or type I toxins

Cause an intense immune response due to release
of cytokines from host cells
Fever, nausea, vomiting, diarrhea, shock, death

Exotoxins
Membrane-disrupting toxins or type II toxins
Lyse hosts cells by:
Making protein channels in the plasma
membrane (e.g., leukocidins, hemolysins)
Disrupting phospholipid bilayer

Cholera
enterotoxin
Vibrio cholerae
Gram (-) comma shaped rods

Exotoxins
Exotoxin

Lysogenic
conversion

A-B toxin type III. Inhibits

protein synthesis.

Streptococcus pyogenes

Membrane-disrupting. Type II
Erythrogenic.

Clostridium botulinum

A-B toxin. Neurotoxin - flaccid

paralysis
Botox

Corynebacterium diphtheriae

C. tetani
Vibrio cholerae
Staphylococcus aureus

A-B toxin. Neurotoxin - prevents

CNS inhibition - spastic
paralysis
A-B toxin. Enterotoxin.
Stimulates cAMP to cause
severe diarrhea
Superantigen. Type I.
Enterotoxin.

Botox
Botulism
Clostridium botulinum
Gram (+), anaerobic, sporeforming rod, found in soil
works at the neuromuscular
junction
prevents impulse from nerve cell to
muscle cell
results in muscle paralysis

Botulus latin word for sausage (first

known as sausage disease) C. botulinum
does not grow in sausage today mainly
due to nitrites added. Infant botulism 250
per yr., most associated with honey due to
little microbial flora in G.I.

Tetanus (Lock Jaw)

Clostridium tetani
Gram (+), spore-forming,
anaerobic rod
neurotoxin acts on
nerves, resulting in the
inhibition of muscle
relaxation
Tetanospasmin spasms or Lock Jaw
50 cases a yr. in U.S.
1 million per yr. Worldwide
50% in newborns because they dress severed umbilical cord with soil, clay or cow dung
Tetanospasmin inhibits the release of acetylcholine by interfering with activity of
cholinesterase (enzyme that normally breaks down acetylcholine)

Endotoxin

Figure 15.4b

Endotoxins

Source

Gram

Metabolic product

Present in LPS of outer membrane

Chemistry

Lipid

Fever?

Yes

Neutralized by antitoxin

No

LD50

Relatively large

Endotoxins - part of the Gram (-) Bacterial cell wall

LPS (Lipopolysaccharides)
O Antigen

Lipid A
Heat Stable (exotoxins are typically heat liable)
Lipid A - Toxin portion of the LPS
responsible for Fever that is associated
with many Gram (-) Bacterial infections
Gram (-) cells are digested endotoxins
are released - fever

Antibiotics
E. coli (0157:H7)
enterotoxin causes a hemolytic inflammation
of the intestines
results in bloody diarrhea

Endotoxins

Figure 15.6

Non bacteria pathogens

Viruses
Protozoa
Fungi
Algae
Helminths

Cytopathic Effects of Viruses

Table 15.4

Pathogenic Properties of Fungi

Fungal waste products may cause symptoms
Chronic infections provoke an allergic response
Tichothecene toxins inhibit protein synthesis
Fusarium
Proteases
Candida, Trichophyton
Capsule prevents phagocytosis
Cryptococcus
Ergot toxin
Claviceps

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Pathogenic Properties of Fungi

Aflatoxin
Aspergillus on peanuts?
Mycotoxins
Neurotoxins: Phalloidin,
amanitin
Amanita death angel
- Liver damage

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Pathogenic Properties of Protozoa

Presence of protozoa
Protozoan waste products may cause symptoms
Avoid host defenses by
Growing in phagocytes
Antigenic variation

Pathogenic Properties of Helminths

Use host tissue

Presence of parasite interferes with host function
Parasite's metabolic waste can cause symptoms
Death can cause excessive immune reaction
leading to more symptoms

Pathogenic Properties of Algae

Neurotoxins produced by dinoflagellates

Saxitoxin
Paralytic shellfish poisoning

Portals of Exit
Respiratory tract
Coughing, sneezing
Gastrointestinal tract
Feces, saliva
Genitourinary tract
Urine, vaginal
secretions
Skin
Blood
Biting arthropods,
needles/syringes

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Mechanisms of Pathogenicity

Figure 15.9