13- Pathogens Flashcards
What are pathogens?
- Microorganisms capable of causing disease (damage to the host).
- Different species have different virulence properties
- Not all strains of a species have the same ability to cause disease.
- A pathogen is usually identified by the set of virulence genes that are carried and expressed.
What is virulence?
- Measure of the ability to cause damage to the host, depends on a number of virulence factors.
- Determined by two basic features (NOT mutually exclusive):
– Invasiveness: the ability of the microorganism to become established in the
host, to overcome the host defenses and to spread in the tissues.
– Toxigenicity: the capacity of the microorganism to produce substances known
as toxins that damage specific 5ssues of the host.
What is invasiveness? What do they use to do so? (5)
• Pathogens use different virulence factors to invade host tissues:
– Adhesins
– Capsules
– Enzymes that destroy host 5ssues
– Invasins
– Type 3 Secretion Systems (T3SS) and Type 4 Secretion Systems (T4SS).
What is adhesin? Fimbriae/pilli? Afimbrial adhesin?
- Promote specific attachment to the host cell surfaces.
- One adhesin type is usually able to attach to one or a few cell types, determine the site of colonization.
• Fimbriae/Pili: polymers, mediate loose
attachment.
• Afimbrial adhesins: (not filaments) mediate close attachment.
What is a capsule?
• Produced by some bacterial pathogens.
• Prevents the pathogen from being
destroyed by host immune cells (phagocytes).
• Also mediates attachment to host cells
and to other bacteria.
• Essential virulence factor for some bacterial pathogens: Streptococcus pneumoniae and Haemophilus influenzae.
• The capsule is not only a virulence factor
(non pathogenic microorganisms may have a capsule too).
Tell me about: Invasion: Destruction of host tissues
Penetration of epidermis: most pathogens use breach in the skin (wounds, surgery, catheter).
Penetration of the mucosa: destruction of the single-cell layer or invasion of cells.
The release of extracellular enzymes: Hyaluronidase, collagenase, lecithinase
- Hyaluronidase: degrades hyaluronic acid, a sticky polysaccharide that holds host cells together. Staphylococci, streptococci, clostridia.
- Collagenase: degrades the protein collagen present in connective tissues (muscle, cartilage).
- Lecithinase: degrades lecithin (phosphatidylcholine) in cell membrane- causes the lysis of red blood cells and destroys tissue cells.
The release of extracellular enzymes: Hemolysins, leucocidin, proteases, coagulase
• Hemolysins: some are enzymes (lecithinase, phospholipase) some are cytolysins (pore-forming). Produced by a great variety of bacteria. Cause lysis of red blood cells and a variety of cell types.
• Leucocidin: causes lysis of leucocytes – white blood cells (WBC) – produced by
staphylococci, streptococci and a few Gram-negatives.
• Proteases: degrade complement proteins and/or antibodies, produced by several bacteria.
• Coagulase : produced by virulent staphylococci; causes insoluble fibrin to be
deposited on bacterial cells and cloaks the bacteria from the immune system.
What is invasins?
- Surface proteins, or injected proteins, that allow microorganisms to enter cells (invade host cell).
- Major virulence factor of intracellular pathogens.
- Invasion of host cells, including phagocytes, protect the bacterial pathogens against the host immune system; good source of nutrients.
• Mycobacterium, Salmonella, Listeria,
Chlamydia
How do pathogen grow inside host cells?
Need to modify the properties and behavior of the host cell:
- Block phagosome maturation (block digestion)
- Increase size of the vacuole
- Acquire nutrients
- Block detection of intracellular infection and response (host defense)
What are the Type 3 and Type 4 Secretion Systems?
• A large number of Gram-negative
pathogens use T3SS or T4SS
• T3SS forms a channel through the bacterial cytoplasmic membrane, the periplasm, the outer membrane, and the host cell membrane so bacterial proteins can be injected into the host cell cytosol.
• Function:
– Invasion of host cells.
– Block phagosome maturation.
– Take control of host cells.
• T4SS: similar to T3SS but absence of
needle-like structure.
• Also called “injectisomes”
Modifies “normal” pathway in the host cells
What is Toxigenicity? 2 categories of diseases? 2 categories of toxins?
• Many pathogens are able to produce toxins that cause damage to the cells.
Extracellular enzymes that cause damage are toxins.
• Toxin production is not always necessary for an organism to be highly virulent.
Damage can be caused by the host’s own immune system or be a result of the large number of pathogens present.
• Bacterial pathogens associated with two distinct categories of diseases:
– Infectious diseases (e.g. pneumonia, meningitis, syphilis): result from the pathogen’s growth.
– Intoxications (e.g. food poisoning): result from the presence of a specific toxin.
• Toxins are divided in two categories :
– Exotoxins (exo = external): secreted into the surrounding as the bacterial pathogen grows
– Endotoxins (endo = internal): part of the bacterial pathogen
What are exotoxins?
• Soluble, secreted or released when the organism is lysed, usually proteins, usually
heat-labile (destroyed by heat).
- Highly immunogenic (antibody response inactivates exotoxins)
- Extremely potent, amongst the most lethal substances known.
• Categorized by their target: – Neurotoxins (nerve tissue) – Enterotoxins (gastrointestinal tract) – Nephrotoxins (kidney) – Hepatotoxins (liver) – Cardiotoxins (heart) – …
- Extracellular enzymes (hyaluronidase, collagenase, …)
- AB toxins
What are AB toxins? What does it do?
Exotoxins
• Modify host cells
• Composed of 2 subunits
– enzymatic subunit (A)
– binding/cell entry (B)
- Subunit A modifies a target inside the host cell leading to damage to the host. Ex: ADP-ribosyltransferase
- Subunit B binds to specific cell receptors providing tissue/cell type specificity.
Give me examples of AB toxins
AB toxin: Botulinum toxin
• Clostridium botulinum
• Neurotoxin – Blocks acetylcholine release in neuromuscular junction – Flaccid paralysis • Affects humans, caUle, horses, ducks…
• “BOTOX”
– Reduces wrinkles / frown
– Muscle spasms
– Hyperhydrosis (excessive sweating)
AB5 Toxins: Cholera toxin
• Infection by Vibrio cholerae is characterized by severe diarrhea, massive loss of fluid from the intestinal tract.
