Topic 8- L2 - Microbial Pathogenesis Flashcards
Infection:
Invasion of body by a disease-causing organism (can by asymptomatic, can result in different disease – not same thing as disease)
Disease:
Damage or injury to host organism (overt symptoms). Some bacteria cause disease without establishing an infection (toxins)
Pathogen:
An organism that causes disease. Pathogenesis: Mechanism that leads to disease
Virulence:
Similar to pathogenicity, but often used to describe the severity of the disease (“highly virulent”)
Opportunistic pathogen:
Typically non-pathogenic organism that becomes pathogen under certain circumstances (e.g. immunocompromised host, access to an open wound)
Inflammation –
body’s immune response to infection or injury - important
part of how we clear infections
Excessive inflammation can have effects from
mild to life-threatening.
Immunocompromised individuals with weakened immune response are
subject to greater risk of infection, more difficulty clearing infections
Major steps in infection / microbial diseases
Adherence, colonization, invasion, spread
For adherence, microbes target specific cell or tissue types such as
Receptors (e.g glycoprotein or glycolipids) on the surface, providing a foothold for invasion
Many types/categorizations of adherence factors:
Pili, fimbriae, adhesins, surface proteins, capsules.
Mucous membranes:
Tightly packed epithelial cell layers covered with a mucous layer. Important protective layer
Mucous membranes line common body access points
(airways, oral cavity, GI tract) and are common places where infections initiated
Invasion:
ability of pathogen to enter host cells and/or tissues. Penetrate beyond where microbes (microbiota) normally reside
Colonization:
Expanding population – Planktonic or Biofilm
Spread:
Moving beyond site of initial infection. Uncontrolled Systemic spread (via bloodstream) often results in very serious infections/disease
An example of an invasion strategy by a pathogen.
S. pyogenes secretes an enzyme called hyaluronidase that degrades hyaluronic acid, a polysaccharide that acts as “cement” to connect some types of host cells. This enzyme can disrupt epithelial layer to facilitate invasion.
Virulence factor:
Molecules (typically proteins) produced by a pathogen that contribute to its ability to cause disease
Nutrient acquisition:
E.g. siderophores, secreted molecules that capture iron from the environment
Immune resistance:
Factors that help pathogen survive immune defenses (e.g. resistance to reactive oxygen species)
Immune evasion/disruption:
Factors that hide microbe from immune system or that disrupt function of immune system
Extracellular enzymes, protein secretion systems/effectors &
toxins :
damage host cells and/or manipulate host cell biology
Many ways that pathogens evade the immune system:
- Hide inside cells (intracellular pathogens)
- Produce a capsule that hides surface antigens (preventing immune detection) & can inhibit uptake and destruction by immune cells
- hide or modify other antigens.
- disrupt immune function/kill immune cells (including toxins, secreted enzymes, secretion systems…)
hide or modify other antigens.
E.g.
pathogen associated molecular patterns (PA M P s ) such as LPS detected by immune system – trigger immune response
Secreted (or surface) enzymes can promote virulence in different ways:
- Provide free up nutrients
- Damage host cells
- Inactivate immune cell mechanisms
- Disrupt barriers to enable pathogen invasion/spread
Examples of secreted enzyme virulence factors that operate by affecting blood clotting. S. aureus secretes
coagulase, which induces clots to prevent immune detection. S. pyogenes secretes streptokinase, which dissolves clots, enabling this pathogen to spread
What type of secretion system used by pathogens
Type III secretion systems
T3SS
T3SS effectors proteins have very specific targets
(often a specific protein) in host cell. Manipulate host cell biology in their favour
Different effectors often have
complementary activities
Exotoxins (“toxins”) are secreted
protein toxins. Similar to bacteriocins
but target host. Amongst the most important virulence factors.
(Not made by all pathogens, other make many)
Example of a bacterial toxin: ⍺-toxin from Staphylococcusaureus toxin proteins
polymerize in host cell membrane to form a pore. This can have a range of effects, from cell lysis to signaling changes. This toxin has a major effect on the virulence of S. aureus strains.
AB-type toxins has two subunits
- A subunit exerts biological effect
- B subunit(s) bind host cell receptor (usually glycoprotein/glycolipid) to mediate uptake
A subunits generally modify or degrade a
specific molecule (or set of very similar molecules) – typically a host cell protein.
AB-type toxin example: Botulinum toxin
produced by Clostridium botulinum. Rarely infects (adult) humans. However - grows/produces toxin on foods we consume
Botulinum toxin
AB-type toxin. B subunit targets
toxin to motor neurons
Botulinum toxin
AB-type toxin. A subunit is a
protease that cleaves specific SNARE proteins that are required by these cells to release the neurotransmitter acetylcholine.
Absence of acetylcholine
release leads to
muscle paralysis
toxoids / toxins
Inactivated toxins as vaccines
Because toxins efficiently, manipulate
human biology in targeted way – can also be used to
treat non-bacterial disease
Botox (botulinum toxin) best example of toxins used for treatment – used to treat range of diseases like
(migraines, cerebral palsy, painful muscle spasms)…in addition to “bunny lines”
Toxins vs. secretion systems
- An important difference between
toxins & secretion systems is that toxins can diffuse and spread to distant cells/tissues. - Toxins often (not Secretion system effector proteins always) more potent, lone wolves. Effectors (often) more nuanced, work together.
Yersinia pestis(plague)
- Gram-negative Proteobacterium
- Primarily a pathogen of rodents. Carried by a disease vector – fleas. Fleas spread disease between rodents.
- spread form person to person (via lice)
Three forms of plague – all caused by same bacterium:
- Bubonic plague (infection of lymph nodes)
- Pneumonic plague (infection of lungs)
- Septicemic plague (bloodstream - rare)
Yersinia pestis - virulence due to ability to
survive/subvert the immune system.
Access infection site (lymph nodes, lungs, blood) & colonize/grow.
Main virulence factors for Yersinia pestis include:
- T3SS injects many different effector proteins into immune cells to inactivate immune functions
- An abundant fimbrial protein that acts as a capsule
- F1 capsule through to inhibit uptake of Y. pestis by immune system & detection of surface antigens
