Chapter 15
Methods of
Microbial Pathogenicity
OR
How the bugs get you!
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Entry into the Host
Pathogens must somehow enter the host in order to cause disease
(obvious???)
Pathogens can enter through several different areas of the body
known as portals of entry
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Common Portals of Entry
Mucous Membranes
Respiratory Tract
Easiest (and most frequent) portal of entry
Inhaled droplets or dust particles containing microorganisms
Respiratory tract entry includes: common cold, tuberculosis,
pneumonia, influenza, and measles
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Common Portals of Entry
Mucous Membranes
Gastrointestinal Tract
Entry by… microorganisms in food and water, contaminated fingers
most are destroyed by acid and enzymes in stomach, surviving
microorganisms cause disease
includes: polio, hepatitis A, typhoid fever, amoebic dysentery, cholera
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Common Portals of Entry
Mucous Membranes
Genitourinary Tract
sexually contracted diseases: includes HIV, genital warts, herpes,
syphilis, gonorrhea
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Common Portals of Entry
Skin
Some microorganisms enter through natural openings in the skin (hair
follicles, sweat glands)
Hookworm larvae (Necator americanus) bore through intact skin
some fungi grow on the keratin of skin or infect the skin itself
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Common Portals of Entry
Parenteral Route
Deposition of microorganisms directly into the tissues beneath the skin
or mucous membranes is called the parenteral route.
examples: punctures, injections, bites, cuts, wounds, surgery, splitting
due to swelling or drying
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Portals & Numbers of Microbes
not all microbes cause disease when they have entered the body -- one
factor can depend on the portal of entry
Salmonella typhi produces disease when ingested, but not when placed
on skin
inhaled Streptococcus can cause pneumonia, but swallowed does not
some microorganisms have more than one successful portal of entry for
disease production (Yersinia pestis)
table 15.1 (next slide) shows some diseases & their preferred POE
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Table 15.1
Preferred Portal of Entry
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LD50 & ID50
Number of invading microbes plays a factor in the onset of disease
virulence or potency of toxins expressed as LD50 – producing death
(lethal dose for 50% of hosts)
dose required to produce demonstrable infection is the ID50
(infectious dose in 50% of hosts)
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Adherence
After entry into a host, almost all pathogens have some method to
attach themselves to host tissue
Adherence is often a necessary step in pathogenicity
Attachment is through binding of surface molecules on the pathogen
specifically to complementary surface molecules on the cells of certain
host tissues (fig. 15.1)
the pathogen's surface molecules are called adhesins or ligands most
are glycoproteins or lipoproteins – they attach to surface molecules on
the host cell.
the surface molecules on the host cell are called receptors
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Bacterial Resistance to Host Defenses
Capsules - bacterial capsules can help resist the host defenses by
impairing phagocytosis (being eaten by host immune system cells)
phagocytic cells cannot adhere to the bacterium
antibodies to the capsule can be made, in which case the encapsulated
bacteria are easily destroyed by phagocytosis
Examples of encapsulated cells include: Streptococcus pneumoniae,
Klebsiella pneumoniae, Hemophilus influenzae, Bacillus anthracis,
Yersinia pestis
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Bacterial Resistance to Host Defenses
Cell Wall Components which aid in resisting defenses
M protein on Streptococcus pyogenes surface mediates attachment and
helps resist phagocytosis
mycolic acids in Mycobacterium tuberculosis resists digestion by
phagocytes
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Enzymes & Increased Virulence
some extracellular enzymes (exoenzymes) produced by bacteria and
ejected from the cell can aid in virulence.
EXAMPLES INCLUDE
leukocidins destroy neutrophils and leukocytes that are active in
phagocytosis (includes staphylococci and streptococci)
hemolysins - bacterial enzymes that cause lysis of erythrocytes (red
blood cells) staphylocci, Clostridium perfringens, and streptococci
streptolysins are hemolysins produced by streptococci (streptolysin O
inactivated by oxygen, streptolysin S has affinity for albumin); both
kinds also lyse white blood cells
(these are some of the enzymes responsible for the hemolysis seen in lab)
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Enzymes & Increased Virulence
coagulases are bacterial enzyme which coagulate the fibrinogen in
blood (cause clotting)
the clots may protect the bacteria from phagocytosis
may also be involved in walling off process of boils produced by some
staphylocci
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Enzymes & Increased Virulence
kinases produced by bacteria break down fibrin and dissolve clots
formed by the body to isolate infections
fibrinolysin (streptokinase) is produced by Streptococcus pyogenes (this
enzyme injected to dissolve some types of blood clots in heart attack
patients)
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Enzymes & Increased Virulence
hyaluronidase is secreted by some bacteria, including streptococci (and
some clostridia involved in gas gangrene) hydrolyzes hyaluronic acid
that holds together certain cells of the body, particularly in connective
tissue. May be involved in blackening of tissue in wounds
helps microorganism spread from initial site of infection
Collagenase - breaks down collagen which forms connective tissue of
muscles and other tissues - produced by species of Clostridium
involved in gas gangrene
lecithinase - destroys plasma membranes
protease - break down proteins, particularly in muscle tissue
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Other Bacterial Substances
Contributing to Virulence
necrotizing factors - kills body cells
hypothermic factors - decreases body temperature
siderophores - scavenge iron from the host's body fluids
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Penetration Into Host Cells
in some cases, attachment signals the host cell to allow the bacterium to
enter the cell
host cell cytoskeleton is responsible for the cytoplasmic movements
which bring the bacterium into the cell (image on next slide)
Salmonella typhimurium and enteropathogenic E. coli produce
invasins, surface proteins that cause rearrangement of actin filaments in
the cell cytoskeleton to bring the bacterium into the cell
once inside cells, some bacteria such as Shigella and Listeria species
can use the actin to propel themselves through the cell and from one
host cell to another
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Damage To Host Cells
Direct damage
can damage cells directly, such as when penetrating cell membranes
or when exiting one cell to enter another (reverse phagocytosis)
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Exotoxins
Toxins: poisonous substances produced by some microorganisms
exotoxins are produced inside the bacterium and then released into
the surrounding medium.
THREE GROUPS
Cytotoxins - kill host cells or affect their function
Neurotoxins - interfere with nerve impulses
Enterotoxins - affect cells in gastrointestinal tract
(Know examples: diptheria, erythrogenic, botulinum, tetanus, vibrio
endotoxin, staphylococcal enterotoxin pp. 442-443)
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Combating Toxins
Antitoxins - are antibodies produced by the body against exotoxins
Toxoids - are inactivated exotoxins injected into the body to produce
immunity
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Endotoxins
Endotoxins are part of the outer portion of the cell wall of Gramnegative bacteria
lipid A, the lipid portion of the LPS of the outer membrane is the
endotoxin
endotoxins are lipopolysaccharides
(reminder - exotoxins are proteins, comparison Table 15.3)
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Gram Negative Cell Wall Details
Useful
Endotoxin!
in recognition
shock & of
fever
some
– blood
strainsor gastrointestinal
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Effects of Endotoxins
responses of the host to endotoxin can include: chills, fever, weakness,
generalized aches, even shock and death (also can induce miscarriage)
pyrogenic response (fever) - see fig. 15.5 (next slide)
shock - life-threatening loss of blood pressure, when caused by Gramnegative organism is called septic shock (tumor necrosis factor
involved in the process
detection of endotoxins - clotting of horseshoe crab blood, Limulus
amoebocyte lysate (LAL) assay
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Pyrogenic Effect – fever production in response to endotoxin
The body responds…
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Plasmids/Lysogeny
virulence factors can be carried on plasmids or lysogenic phages
(shared DNA)
plasmid encoded:
tetanospasmin, heat-labile enterotoxin, staphylococcal enterotoxin and
others
phage encoded:
lysogenic phages are incorporated in the bacterial cell's chromosome
changes in the characteristics of the cell are called lysogenic conversion
includes diphtheria toxin, botulinum neurotoxin, choleratoxin
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Non-Bacterial Pathogens
Viruses
evade destruction by the host's immune response by:
penetrate into the cell, where they are not available to the immune system
attachment sites mimic useful substances of the cell
damage cells (cytopathic effects) by damaging plasma membrane, inhibiting
DNA, RNA or protein synthesis (table 15.4)
inclusion bodies are granules sometimes produced in infected cells
synctium - infected cells which fuse (caused by paramyxoviruses)
interferon is produced by infected cells, helps adjacent cells avoid infection
loss of contact inhibition caused by viral transformation
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Other Pathogens
Fungi
metabolic products (ergot, aflatoxin, mycotoxins)
direct infections
Protozoa
presence of protozoa and waste products produce disease symptoms
antigenic shifts (Trypanosoma)
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Other Pathogens…
Algae
neurotoxins (e.g.paralytic shellfish poisoning)
Helminths
presence in host produces disease symptoms
block of circulation (elephantiasis)
toxic or noxious waste products
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