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Microbial Mechanisms of
Pathogenicity
In other words, how do pathogens
actually make us sick?
How does a pathogen get into
your body?
•  Portals of entry are the specific routes by which
pathogens enter the body.
•  The Integumentary System protects you and surrounds
your body entirely. It is also, by necessity, the site of
entrance of the pathogen, one way or another.
•  Mucous membranes
–  Respiratory tract - if pathogen is inhaled; this is the most
susceptible membrane and the most common portal of entry
–  Urogenital tract - often via sexual intercourse
–  Gastrointestinal tract - food, water, contaminated fingers
The skin (the cutaneous membrane)
•  Intact skin is usually an effective barrier to
the entry of pathogens; sometimes they can
colonize sweat ducts or hair follicles.
•  If a pathogen is introduced through the skin
via injection, insect bite, or the presence of
a wound, we refer to this as the parenteral
route.
Preferred Portal and Adherence
•  Some pathogens will only cause disease if they
enter the body through their preferred portal of
entry (e.g., certain Streptococci that are inhaled
can cause pneumonia but if swallowed have little
effect).
•  Once entry is gained, pathogens need to attach to
host tissue, a process called adherence.
How do bacterial pathogens
penetrate host cell defenses?
•  Capsules contribute to virulence because they can
protect against phagocytosis.
•  Sometimes components of the cell wall can have a
similar effect.
•  Enzymes produced by pathogenic bacteria can do
amazing things...
Bacterial Enzymes and other proteins
which contribute to virulence
•  Leukocidins destroy neutrophils and macrophages
(phagocytosing cells) - Staph and Strep often make
them
•  Hemolysins lyse red blood cells (and sometimes
white blood cells)
•  Coagulases cause blood to clot, protecting and
isolating the bacterium from host defenses common in Staph
•  Mucinases, keratinases, and collagenases digest or
dissolve mucus, keratin, and collagen, respectively.
How do bacteria damage you?
•  Direct damage - Quite simply, host cells can be
harmed or destroyed if bacteria are growing and
metabolizing in or around them.
•  Most bacterial damage, however, is due to the
production of TOXINS (poisonous substances).
•  There are two major groups of toxins: exotoxins and
endotoxins.
–  Exotoxins are produced as by-products of bacterial
metabolism and are released into the host.
–  Endotoxins are part of the cell wall; they are liberated
only when the bacteria die and the cell walls are
degraded.
Exotoxins
•  Proteins mainly produced by gram-positive cells.
•  Affect the host in a specific way:
–  Cytotoxins kill host cells or render them inactive
(example: Diphtheria toxin inhibits protein synthesis
in host cells)
–  Neurotoxins interfere with the transmission of nerve
impulses (examples: botulinum and tetanus toxins)
–  Enterotoxins adversely affect cells lining the
gastrointestinal tract (example: Vibrio and Staph
toxins)
–  Antibodies produced against these toxins are called
antitoxins.
Endotoxins
•  Lipopolysaccharides that are part of the cell wall;
mainly present in the outer membrane of
gram-negative bacteria, remember LIPID A?
•  The death of the bacterial cell liberates the toxin as
the outer membrane and cell wall break down.
•  The immune system’s actions may cause the cells
to die, or ironically antibiotics may be the cause.
•  Regardless, when the endotoxins are released, they
all generally affect the body in a similar fashion.
Endotoxins
•  Cause chills and fever (the pyrogenic response) due to
the stimulation of production of interleukin-1 by
macrophages. This causes the hypothalamus (which
controls body temperature) to reset the body’s
thermostat.
•  Can cause shock (loss of blood pressure), in this case
called septic or endotoxic shock, due to systemic
inflammation that involves blood vessel dilation. This
leads to a drop in blood pressure and can be fatal.
•  Effective antibodies are usually not made against
endotoxins. They have a certain half life, and will
produce minor to major effects (but all generally of the
same type).
Viruses
•  Since viruses reproduce inside host cells, they can
avoid certain aspects of the defense system.
•  Viruses cause cytopathic (cell+disease) effects
(CPE), which may cause cell death (cytocidal) or
damage (noncytocidal).
•  Interferons are chemicals produced by host cells
to protect against viral infection.