Post on 05-Jan-2016
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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.
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 endocytosis2) Fusion of vesicle with lysosome3) Acid environment of lysosome reduces disulfide bonds and releases A into cell4) A has various cellular activities
Bacterial Exotoxins
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.
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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