Download Virulence Factors of Pathogens Toxin: Botulism toxin Botulism: case

LECTURE 20
Virulence Factors and Pathogenesis
Virulence Factors of Pathogens
Virulence Factors of Pathogens
• Substances generated by pathogens that
enhance their ability to cause disease
• Four categories of virulence factors
correspond to the different mechanisms
pathogens used to cause disease
Toxin: Botulism toxin
• Botulism toxin (tan) snakes around the
SNARE protein – a protein important in
the transmission of nerve impulses. Toxin
cleaves SNARE; results in paralysis.
Colonization of surface, followed by
toxin production
• V. cholera
– Toxin activates host epithelial transmembrane pump to cause Clefflux, with H2O following
– Up to 15-20L fluid loss; if 7% loss of body wt, requires IV fluids
• B. pertussis (whooping cough)
– Attach to ciliated epith, toxin causes release of NO fm goblet cells
– Kills ciliated epithelial cells
• Four categories
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–
–
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Toxins
Adhesion Factors
Evasive Factors
Invasive Factors
• Often encoded in pathogenicity islands
– Generally mobile genetic elements or have evidence of having
been mobile element
Botulism: case study
• 2003 – Pumpkin butter
– Non-acidic food source
– Possible contamination with spores fm
soil
– Pumpkin butter consumed quickly – no
disease
– Pumpkin butter consumed later –
disease, paralysis
– Wrinkles?
Invasion of host tissue
• Organisms penetrates host defenses and multiplies within
tissues
• Can then avoid host detection / destruction
– M. tb survives in macrophages
• Invasion facilitated by thwarting host defense
– S. pyogenes binds to constant regions of antibodies, antibodies
unrecognizable by phagocytes.
Invasion of host tissues, then
produce toxin
• Differs fm strategy #2 b/c organisms
actually invade tissues
Establishment of infection
• Adherence
• Colonization
– Shigella – invades intestinal cells, toxin stops
translation, infected host cells die
– Massive inflammatory response, leaky gut,
dysentery
– Spread of organisms facilitated
Adherence
Adherence
• Adhesins – located on tips of pili or is component of
glycocalyx or cell walls
– Generally, glycoproteins or glycolipids
– Binding is specific
• Ex: E. coli c plasmid encoding other adhesins allow adherence to
bladder epithelial cells
• Hemagglutinins on viruses that recognize receptors on
cells in upper respiratory tract
– Typing makes up part of categorizing flu strains
Figure 19.3
Colonization
• Prereq for disease state = multiplication;
orgs must multiply in order to be
transmitted / result in disease
– Tetanus – needs to germinate
• Needs to compete with normal flora (space,
nutrients, overcome toxicity, overcome host
defenses)
Colonization
• Rapid turnover of pili (slough off bound antibodies to
adhesins)
• Antigenic variation
• IgA protease (S. pneum., N. gonorrhea, a Clostridia
spp, H.infl B.)
• Siderophores
– Importance of Fe availability – signals to a microbe that they
have entered the host tissues
Invasion
• Penetration of skin
• Penetration of mucous membranes
– Many intestinal pathogens
– Many upper respiratory tract pathogens
– Many STI’s
Penetration of Mucous
Membranes
Penetration of skin
• Trauma
– Deep wounds for C. tetani
• Arthropods
– West Nile Virus, Yellow Fever
- mosquitoes
– Lyme – ticks
Penetration of mucous membranes
• Induction of non-phagocytic uptake of
themselves via endocytosis
– Via type III secretion systems to induce host
cell cytoskeletal changes to induce uptake
(Shigella, Salmonella)
Avoiding the host defenses
•
•
•
•
Hiding within a host
Avoiding complement proteins
Avoiding phagocytes
Avoiding antibodies
Hiding Within a Host Cell
• Shigella – within intestinal ciliated
epithelial cells and
• TB hides initially in alveolar macrophages
Self molecule mimicry:
S. pyogenes – capsule composed of hyaluronic
acid
Damage to the host
• Exotoxins
• Endotoxins
• Immune response
• Hyaluronic acid – polysaccharide found
in host tissues.
S. pyogenes – exotoxins,
most facilitate invasion
Exotoxins
A-B toxin,
as in
diphtheria
• Streptokinase (fibrinolysin) – clot buster
(facilitates invasion)
• Streptodornase (strep DNase) – destroys host
DNA; contributes to viscosity of pus
• Hyaluronidase – splits hyaluronic acid, component
of connective tissue; contributes to spread
• Diphosphopyridin nucleotidase – kills leukocytes,
prevents destruction of bacteria
Figure 19.12
Endotoxins – G -, Lipid A
Endotoxin – Lipid A
• Do not contain proteins, not actively
released from bacteria during growth, have
no enzymatic activity
• Sm amt = potent activator of physiologic
responses
• Recognized by phagocytes, which then
secrete cytokines – results in physiologic
response
Figure 19.14