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Transcript
Mechanisms of Pathogenicity
Introduction
Entering the Host
Penetrating Host Defenses
Damaging Host Cells
Pathogenicity - Introduction
Pathogenicity is the ability of a
pathogen to produce disease by
overcoming host defenses
 Virulence is the degree of pathogenicity

– Expressed as LD50 (lethal dose necessary to
kill 50% of the inoculated hosts)
– ID50 is also used (dose necessary to infect
50% of the inoculated hosts)
Pathogenicity – Entering Host
Route of entry is called Portal of Entry
 Usual portals include mucous
membranes

–
–
–
–
Conjunctiva (eyes)
Respiratory tract
Gastrointestinal tract
Genitourinary tract
Pathogenicity – Entering Host

Respiratory most common
– Microorganisms are inhaled on moisture
droplets or dust particles
Genitourinary through mucous
membranes and direct contact
 Gastrointestinal through food, water
and contaminated fingers

Pathogenicity – Entering Host
Most microorganisms cannot penetrate
skin but can gain access through hair
follicles and sweat ducts
 Can gain entry through inoculation also
called parenteral

– insect bites
– injections
– wounds
Penetrating Host Defenses

Bacterial Elements that Overcome Host
Defenses
–
–
–
–
Capsules
Cell Wall Components
Enzymes
Cytoskeletal Components
Penetrating Host Defenses

Capsules
– Prevent or reduce phagocytosis
– Usually polysaccharide
– Examples
» Dextran (S. mutans)
» Polyglutamic acid (B. anthracsis)
Penetrating Host Defenses

Cell Wall Components
– Adhesins (adhere to complementary
receptors on host cells
– Fimbriae – interact with membrane
glycoproteins especially mannose
– Some microbes reproduce only in host cells
Penetrating Host Defenses

Enzymes
–
–
–
–
Leukocidins – destroy white blood cells
Hemolysins – destroy red blood cells
Kinases – digest blood clots
Hyaluronidase – digests
mucopolysccharides
– Collogenase – destroy collogen of
connective tissue
Penetrating Host Defenses

Via Cell Cytoskeleton
– Invasins
– Cause actin of microfilaments to form
basket to carry bacteria into cell
– Found in Salmonella
Damaging Host Cells
Damage by metabolizing and
reproducing in hosts
 Damage by the production of toxins
 Two major types of toxins

– Endotoxins
– Exotoxins
Damaging Host Cells

Exotoxins
– Usually from Gram positive bacteria
– Usually a secreted protein product
– Heat Labile (60 to 80 deg C)
– Very toxic – low LD50
– Usually specific for cell type or cell
function
– Can be neutralized by antibodies
– Symptoms usually appear sooner
Damaging Host Cells

Exotoxins – Examples
– Diptheria toxin –stops protein sysnthesis;
damages heart and other organs
– Cholera toxin – affects intestinal cells;
disrups cAMP a cell secondary messenger
– Tetnus toxin – affects nerve transmission
– Toxic shock –affects T-cells & macrophages
– Listeriolysin – pore forming cytotoxin
allows cell to escape phagocytic vesicle
Damaging Host Cells

Endotoxins
– Almost exclusively Gram negative
– Present in LPS and released with
destruction of cell
– Heat stable – often can withstand autoclave
– Not easily neutralized by antibodies
– Produces general effects fever, aches, shock
– Much larger LD50 than exotoxins
Damaging Host Cells

Endotoxins – Examples
– Salmonella typhi and typhoic feverincubation period ~ 1 week symptoms due
to LPS induced release of cytokines enter
blood and multiply in spleen and liver
– S. enteriditis & S. typhimurium – food borne
gastroenterits – symptoms usually appear
within 24 to 48 hours takes longer than
with S. aureus exotoxin