Microbial Mechanisms of
Pathogenicity
• Virulence is the degree of pathogenicity of
an organism.
• Pathogenicity, Ability to cause disease.
Portals of entry are usually
constant for a microbe
• Mucous membranes of conjunctiva,
respiratory, gut and genitals
• Inhalation of dust and moisture particles to
lungs
– This is the most common entryway
• Skin is hard to penetrate
– Most enter through hair follicles and sweat
ducts
– Some fungi may attach to skin cells.
• Microbes gain access to systemic system
through
– Bites
– Injections
– Wounds
– Called parenteral rout
Preferred Portal of entry
• Most cause infection only when they use a
specific portal of entry
• Example
– Yersinia pestis by a number of portals
– Streptococcus pneumoniae respiratory tract
– Vibrio cholerae gut
– Neisseria gonorrhoeae genitals
– Clostridium perfringes parenteral
Lethal and infectious doses, the
number of invaders determines
what the outcome may be
• LD50 # to kill 50% of inoculated individuals
• ID50 # to cause infection in 50%
• Is basically a method to compare relative
toxicities or conditions
Bacillus anthracis
Portal of entry
ID50
Skin
10-50 endospores
Inhalation
10,000-20,000 endospores
Ingestion
250,000-1,000,000
endospores
Adherence
• In order to get into a host the bacteria
must stick to it.
• Surface projections (ligands) adhere to
receptors on host cells.
• Mostly on structures called fimbriae
• The sugar mannose is the most common
receptor.
Adherence
• Adhesions/ligands bind to receptors on host
cells
– Glycocalyx
– Fimbriae
– M protein
– Opa protein
– Tapered end
Streptococcus mutans
Escherichia coli
Streptococcus pyogenes
Neisseria gonorrhoeae
Treponema pallidum
How Bacteria escape programmed
host defenses
• Capsules are extracellular glycocalyx
material that surrounds the cell. Prevent
recognition of the bacterial cell.
Streptococcus pneumoniae
• Cell wall components may also resist
recognition and phagocytosis
Enzymes that protect
• Leukocidins destroy neutrophils and
macrophages
• Hemolysisn break up red blood cells
• Coagulase prevents or breaks up blood
clots designed to localize infection
• IgA proteases
Destroy IgA antibodies
Bacteria moving into tissues
• Kinases- destroy blood clots
• Hyaluronidase works on
mucopolysaccharide that holds cells
together
• Collagenase hydrolyses connective tissue
collagen
• Invasins destroy cytoskeleton of individual
cells.
How bacterial pathogens damage
the host cells.
• Only some of the cell damage is caused
by bacteria themselves
– Some bacteria enter the host cell and damage
as they leave
– Some bacteria harm the cell as they enter
Penetration into the Host Cell
Figure 15.2
Bacteria Toxins
• Cause the most damage
• Toxins: poisonous substances produced by
microbes
• Toxigenicity: capacity of a microbe to produce
toxin
• Toxemia: presence of toxins in the blood
• Toxoid: Inactivated toxin used in a vaccine
• Antitoxin:Antibodies against a specific toxin
Exotoxins:
• Produced by bacteria and released into
surrounding area. Causes Disease
– Cytotoxin or diphtheria toxin inhibits protein
synthesis
– Tetanus toxin prevents nerve transmission
– Enterotoxins promote electrolyte and fluid
loss from cells.
– Neurotoxins (Botulinum toxin) prevent nerve
transmission
– Antibodies produced in response are
antitoxins
Exotoxin
Source
Metabolic product
Chemistry
Fever?
Neutralized by
antitoxin
LD50
Mostly Gram +
By-products of growing cell
Protein
No
Yes
Small
Exotoxins
• A-B toxins
or type III
toxins
Figure 15.5
Exotoxins
• 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
Exotoxins
Exotoxin
Lysogenic
conversio
n
A-B toxin. Inhibits protein
synthesis.
+
• Streptococcus pyogenes
Membrane-disrupting.
Erythrogenic.
+
• Clostridium botulinum
A-B toxin. Neurotoxin
+
• C. tetani
A-B toxin. Neurotoxin
• Vibrio cholerae
A-B toxin. Enterotoxin
• Corynebacterium
diphtheriae
• Staphylococcus aureus
Superantigen.
Enterotoxin.
+
Endotoxins
Figure 15.6
Endotoxins
• Are structures of the bacterium itself that
cause the disease, like lipopolysaccharide
(LPS) of gram negative bacteria
– May be released when cells are killed by
antibiotics
– Cause fever and shock
– May allow the bacteria to cross the blood
brain barrier
A test for endotoxins.
• Limulus amoebocyte lysate (LAL) used to
detect endotoxins in drugs and on medical
devices.
– The amoebocyte will lyse in the presence of
endotoxins causing a thickening of the media.
Endotoxins
Source
Metabolic product
Chemistry
Fever?
Neutralized by
antitoxin
LD50
Gram–
Present in LPS of outer
membrane
Lipid
Yes
No
Relatively large
Extra genetic material
• Some bacteria may carry extra genes that
help pathenogenisity
– Plasmids (extra chromosomal) can carry
genes for antibiotic resistance, toxins,
capsules and fimbriae
– Coagulase produced by Staphylococcus
aureus
– Fimbria in specific straines of E. coli
•
Pathogenesis of nonbacterial
microbes
Viruses
– Avoid immune system by growing inside host cell
– May cause cell death or damage by growing and
being released from the cell.
– Casuse membranes to fuse
• Fungi, Protozoa, Helminths and Algae
– Symptoms caused by mixture of capsules, toxins,
waste products and allergic response to the organism
– Antigen switching allows to avoid hose immunity
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