Mechanism of Pathogenicity
Pathogens & Disease
Pathogens are defined as microbes
capable of causing host damage.
 When host damage reaches a certain
threshold, it can manifest itself as a
disease.

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The evolution of an infectious disease in an
individual involves complex interactions
between the pathogen and the host.
PATHOGENICITY & VIRULENCE

Pathogenicity – the ability to cause disease by overcoming the
defenses of the host

Virulence – the degree or extent of pathogenicity

Virulence factors – the various traits or features that allow or
enhance the microorganism’s ability to cause disease. These
take may forms and include:
adhesion organelles,
toxin production,
evasion of the host’s immune response,
resistance to antibiotics,
ability to invade host tissues
MECHANISMS OF PATHOGENICITY
Portal of Entry
Adherence
Penetration/invasion
of host defense
Damage to host cell
PORTALS OF ENTRY

To cause disease, most pathogenic bacteria must gain
access to the host

including skin and mucus membranes

cuts, surgical procedures, catheters, etc may allow
bacteria entrance into the host

Normal skin flora, including Staphylococcus aureus and
Staphylococcus epidermidis, can enter through these
barriers and establish an infection
PORTALS OF ENTRY

Many pathogens have preferred portals of entry that are
necessary for disease production

If they gain entrance via another portal, disease may not
occur
 Salmonella typhi produces disease when swallowed but
not if rubbed on the skin
 Streptococci that are inhaled can cause pneumonia but, if
swallowed, generally do not produce disease
 Bacillus anthracis can initiate disease from more than one
portal of entry (skin inoculation, GI, respiratory)
ADHERENCE.
Means attachment
 A necessary step in pathogenicity
 Attachment between pathogen and host
is accomplished by means of adhesins or
ligands.
 Most adhesins of microbes are
glycoproteins or lipoproteins

ADHERENCE

The term pili (pilus) is also used to bind the host
cells

Gram positive organisms use other structures for
adhesins (lipoproteins, etc). Streptococcus pyogenes
uses lipoteichoic acid to bind to epithelial cells

Once attached to target cells, many bacteria can then
invade the cell
ADHESINS ARE VERY DIVERSE.

S. mutans plays a key role in tooth decay
attaches to the surface of teeth by its
glycocalyx

E. coli have adhesins on fimbriae that
adhere only to specific kinds of cells
INVASION

Not all bacteria are invasive. Invasive organisms
attach and enter host cells by a number of
mechanisms:
 Production of surface proteins called invasins
 Production of enzymes:

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collagenase which breaks down collagen in connective
tissue
hyaluronidase which breaks down hyaluronic acid that holds
cells together (particularly connective tissue cells)
Coagulase which converts fibrinogen to fibrin producing a
clot (may be protective against phagocytes)
Kinases which can break down clots decreasing the isolation
of bacteria in clots (spreading effect)
HOW BACTERIA DAMAGE HOST CELLS.

Direct damage

The production of Toxins
Types of toxins: Exotoxins and Endotoxins.
Bacterial Toxins

Many different types of toxins



Exotoxins
Endotoxins
Toxins are are not required for growth

Genes for toxins are usually on plasmids
EXO and ENDOTOXINS.
EXOTOXINS.

Produced inside some bacteria as part of their
growth and metabolism and released into the
surrounding medium

Are proteins, and many are enzymes

Most bacteria that produce exotoxins are grampositive

The genes for most exotoxins are carried on
bacterial plasmids or phages.
Neurotoxin.

Target the nervous system, and can
interfere with normal nerve impulse
transmission, e.g. C. tetani, C. botulinum.
ENTEROTOXINS.
Affect cells lining the gastrointestinal tract.
 E.g. V. cholerae, C. difficile.

ACTION OF AN EXOTOXIN.
Bacterial Exotoxins

Exotoxins




Initial location outside
cells
Transported into host
cells
Alter host cell
physiology and
metabolism
Typical A – B toxins
AB toxin enters cells via:
1) Receptor mediated endocytosis
2) Fusion of vesicle with lysosome
3) Acid environment of lysosome
reduces disulfide bonds and
releases A into cell
4) A has various cellular activities
Corynebacterium diphtheriae

Corynebacterium diptheriae




Produces AB exotoxin
Gram positive rod
Significant cause of mortality until 1950s
Common location upper respiratory tract
Clostridium botulium

Clostridium botulinum

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Produces AB exotoxin
Produces irreversible muscle relaxation
Flaccid paralysis
Symptoms result entirely from toxin
Anaerobic gram + rod
Usually ingested in contaminated food
Does not involve fever or sepsis
Patients die of paralysis and respiratory failure
Normal Neuronal Signaling
Mechanism of Action of botulinum toxin
NOTABLE EXOTOXINS.
Diphtheria toxin.
 Erythrogenic toxins.
 Botulinum toxin.
 Tetanus toxin
 Vibrio Enterotoxin.
 Staphylococcal Enterotoxin.


.
Bacterial Endotoxins

Endotoxins


Toxin is not internalized
Toxin is located on outside of microorganisms (Part of
the outer portion of the cell wall of bacteria)
 LPS of gram – bacteria
 Lipoteichoic acid or gram + bacteria


Only toxic at high levels
Liposaccharide

Exert their effects when the gram negative
bacteria dies and their cell wall undergo
lysis, thus liberating the endotoxin(e.g use
of antibiotics)

All endotoxins produce the same signs and
symptoms

Endotoxins can also induce miscarriage.
Mechanism of Action of Endotoxins

Endotoxins bind to

Receptors on

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Macrophages
Neutrophils
Lymphocytes
Proteins of complement



Complement is a group of proteins which circulate at
constant levels in the blood
When activated complement is a powerful tool
against invading pathogens
Increased inflammation
Bacterial Endotoxins

Endotoxins


Host cell receptors (TLR) bind to
components of pathogen
Pathogen associated molecular
patterns PAMPS



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LPS – gram - cell walls
Flagella
Lipoteichoic acid – gram + cell
walls
Signal transduction pathways
begin to make a cellular response

Production of cytokines
Bacterial Exoenzymes

Enzymes secreted by bacterial cells into
the extra cellular matrix of host

Membrane Damaging Toxins

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Enzymes which act in the extra cellular matrix

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Enzyme destruction of host cell membranes
Lyse red blood cells
Membrane pore forming complex
Spreading factors
Breaks down connective tissue
Attacks blood clots
Enzymes which subvert drug therapy in
patients

Penicillinase
Some Common Exoenzymes

α toxin



Pore forming toxin
Common in
Staphylococcus aureus

Destroy red blood cells
Streptolysins – group of
hemolysins excreted by
Streptococcus
Streptokinase


Attacks fibrin clots
From Streptococcus
pyogenes
Hyaluronidase

Hemolysins


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Breaks down hyaluronic
acids in connective
tissue
Similar function for

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Collagenase
Elastases
DNase

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DNA is viscous
Thins pus (DNA &
debris) released from
WBC
Clostridium perfringens

Clostridium perfringens

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Ananerobic gram + spore forming rod
Widely distributed in nature
Entry of spores by traumatic injury
Not highly invasive so it requires exoenzymes for a
supportive growth environment
Exoenzymes

Lecithinase lipase c – major toxin
 Lyses mammalian cells indiscriminately
 Substrate is phophatidylcholine

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Collagenase & hyaluronidase
DNAase