Microbial Mechanisms Of Pathogenicity Cont. Lecture 15 Flashcards
Stages of Pathogenesis
- Exposure
- Adhesion
3.invasion
4.infection
Exposure (contact)
The site where a pathogen passes into the body is the portal
of entry
– Major portals of entry:
• Mucous membranes
• Skin
• Parenteral routes – breaks in skin
• Placenta (TORCH infections)
Adhesion
Some have proteins or sugars called adhesins that allows
the pathogen to attach to glycoprotein receptors on host cell
• In bacteria: found on fimbriae, flagella
• In protozoans, found on cilia
• In viruses, found on membranes or capsids
– Glycocalyx aides bacterial adhesion
– Some protozoans also use hooks or barbs
– Some viruses also use spike proteins
– Biofilms also aid in adhesion, and offer protection from
immune cells and antibiotics
Invasion
After adhesion, pathogens often disseminate throughout local tissues in the host
This process may involve the production of toxins or enzymes that
damage host tissues to aid in tissue invasion
– Intracellular pathogens enter the interior of host cells
Infection
After invasion, a pathogen that successfully reproduces in
the host leads to infection
• A local infection is confined to a small area of the body, usually near
the portal of entry
– Pneumonia, boils & pustules, urinary tract infections
• A focal infection is where effects of a local infection spread to other
locations
– Oral Streptococcus spp. introduced into the bloodstream during dental
procedures can cause an infection of the heart valves
• A systemic infection is one that is disseminated throughout the body
– Varicella, septicemia
• A secondary infection is one that happens because a primary
infection has weakened the host
Transmission of infection
transmitted to a new host through a
portal of exit
Skin, and urogenital, respiratory, gastrointestinal tracts
– Aerosolized droplets
– Feces
– Urine
– Semen
– Vaginal secretions
– Tears
– Sweat
– Shed skin cells
Virulence factors
Virulence factors are often unique to individual pathogens
• Generally, are toxins, proteins, enzymes and other molecules that enhance the ability of the pathogen to cause disease
Virulence factor adhesion
Virulence factors for adhesion aid in the first step of pathogenesis
- ex finbrial adhesion found on the tips of finbrae on ecoli
Virulence invasion
After adhesion, some pathogens secrete exoenzymes
or toxins to aid in invasion
• Exoenzymes enable a pathogen to invade deeper into
tissues
Virulence Factors: Exoenzymes
Hyaluronidases
This enzyme degrades hyaluronan (hyaluronic acid),
an adhesive-like molecule that holds connective tissue
cells together
Virulence Factors: Exoenzymes
DNAses
This enzyme degrades DNA that is released into the
environment when a host cell dies
Virulence Factors: Exoenzymes
Phospholipases
destroys the phospholipid bilayer of the phagosome before it can fuse with a lysosome
Also involved in hemolysis
Virulence Factors: Exoenzymes
Proteases
These are protein-digesting enzymes
Virulence Factors: Toxins
Toxins also damage host cells, assist in ability of
pathogens to invade host tissues
• Are found as exotoxins or endotoxins
Virulence Factors: Endotoxins
• Endotoxins are toxins that are integral to the pathogen, not secreted into the environment
Virulence Factors: Endotoxins
Lipopolysaccharide heat stable
Lipopolysaccharide, found on the outer membrane of
Gram negative bacteria, is an endotoxin
Virulence Factors: Endotoxins
Lipid A heat stable
the toxic portion of this molecule, triggers the host’s immune system inflammatory response
• Ordinarily helpful, the inflammatory response can
become life-threatening when high levels of lipid A
trigger an overreaction
Virulence Factors: Exotoxins
Exotoxins are toxins that are secreted into the environment around the pathogen
Most exotoxic bacteria are Gram positive
• Act more specifically than endotoxins, often targeting
specific cell receptors on host cells
• Very small amounts can be highly toxic
Virulence Factors: Exotoxins
Intracellular-targeting toxins (A-B toxins)
The B unit targets specific cell receptor(s) and binds them
– The A-B toxin is then brought into the cell by endocytosis
and vacuolized
– The A unit separates when the vacuole is acidified and
enters the cytoplasm
– A unit then interferes with specific cell function that it is
targeted to
Examples of A-B toxins
Diphtheria toxin- stops elongation in protein synthesis and kills the cell
Cholera toxin - The high level of the cAMP secondary messenger causes
excessive secretion of fluids and electrolytes into the
intestinal lumen
Botulinum toxin- Is a neurotoxin that
Causes a catastrophic flaccid paralysis that can result in death
Tetanus toxin - Causes a contractile paralysis that can result in death
Virulence Factors: Exotoxins
Membrane-disrupting toxins
Hemolysins and leukocidins form pores in the membranes of red blood cells, white blood cells, an some other cell types
(Streptococcus pyogenes and others)
Virulence Factors: Exotoxins
Superantigens
Act by triggering an excessive, non-specific stimulation of immune cells to secrete cytokines (chemical messengers)
Cytokine storm:
can cause life threatening high fevers, low blood pressure, multi-organ failure,
shock, and death
