Chapter 15

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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 microbe’s 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 host’s 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
other end.
• Clostridium
botulinum
•
Spread by contaminated hands &
fingers or contaminated food &
water
•
Poor personal hygiene.
Mucous Membranes of the Genitourinary System - STD’s
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 it’s 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
Skin
ID50
??? 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 won’t 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
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (LZW) decompressor
are needed to see this picture.
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
Coagulate blood - wall off from host
make boil
• Kinases
Digest fibrin clot - allow
spreading
streptokinase and staphylolinase
• Hyaluronidase
Hydrolyses hyaluronic
acid connective tissue
• Collagenase
Hydrolyzes collagen
• IgA proteases
Destroy IgA antibodies
• Hemolysins
lyse RBC’s
Hemolysins
Alpha Hemolytic Streptococci
- secrete hemolysins that cause the incomplete
lysis or RBC’s
Beta Hemolytic Streptococci
- secrete hemolysins that cause the complete lysis of
RBC’s
Leukocidins
• Enzymes that attack certain types of WBC’s
• 1. Kills WBC’s 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
Fever?
Neutralized by antitoxin
LD50
Mostly Gram +
By-products of growing cell
Protein
Water soluble
No
Yes
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 host’s 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
• Corynebacterium diphtheriae
• Streptococcus pyogenes
• Clostridium botulinum
• C. tetani
• Vibrio cholerae
• Staphylococcus aureus
Exotoxin
Lysogenic
conversion
A-B toxin type III. Inhibits
protein synthesis.
+
Membrane-disrupting. Type II
Erythrogenic.
+
A-B toxin. Neurotoxin - flaccid
paralysis
Botox
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Pathogenic Properties of Fungi
• Aflatoxin
• Aspergillus on peanuts?
• Mycotoxins
• Neurotoxins: Phalloidin,
amanitin
• Amanita “death angel”
- Liver damage
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
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
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Mechanisms of Pathogenicity
Figure 15.9
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