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.
 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:
 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 gram-

positive

 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
 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
 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
 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
 Enzyme destruction of host cell membranes
 Lyse red blood cells
 Membrane pore forming complex
 Enzymes which act in the extra cellular matrix
 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
 Hemolysins
 Destroy red blood cells
 Streptolysins – group of
hemolysins excreted by
Streptococcus
 Streptokinase
 Attacks fibrin clots
 From Streptococcus
pyogenes
 Hyaluronidase
 Breaks down hyaluronic
acids in connective
tissue
 Similar function for
 Collagenase
 Elastases
 DNase
 DNA is viscous
 Thins pus (DNA &
debris) released from
WBC
Clostridium perfringens
 Clostridium perfringens
 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
 Collagenase & hyaluronidase
 DNAase