Mechanism of Pathogenicity

1
Mechanism of Pathogenicity
2
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.

3
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
  microorganisms ability to cause disease. These
  take may forms and include
• adhesion organelles,
• toxin production,
• evasion of the hosts immune response,
• resistance to antibiotics,
• ability to invade host tissues

4
MECHANISMS OF PATHOGENICITY
Portal of Entry
Adherence
Penetration/invasion of host defense
Damage to host cell
5
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

6
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)

7
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

8
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

9
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

10
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)

11
HOW BACTERIA DAMAGE HOST CELLS.

• Direct damage
• The production of Toxins
• Types of toxins Exotoxins and Endotoxins.

12
Bacterial Toxins

• Many different types of toxins
• Exotoxins
• Endotoxins
• Toxins are are not required for growth
• Genes for toxins are usually on plasmids

13
EXO and ENDOTOXINS.
14
(No Transcript)
15
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.

16
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.

17
ACTION OF AN EXOTOXIN.
18
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
19
(No Transcript)
20
Corynebacterium diphtheriae

• Corynebacterium diptheriae
• Produces AB exotoxin
• Gram positive rod
• Significant cause of mortality until 1950s
• Common location upper respiratory tract

21
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
  

22
Normal Neuronal Signaling
23
Mechanism of Action of botulinum toxin
24
NOTABLE EXOTOXINS.

• Diphtheria toxin.
• Erythrogenic toxins.
• Botulinum toxin.
• Tetanus toxin
• Vibrio Enterotoxin.
• Staphylococcal Enterotoxin.
• .
• .

25
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

26

• 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.

27
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

28
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

29
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

30
Some Common Exoenzymes

• a 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

31
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