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General Microbiology II

Microbial Interactions with Humans (Host-Parasite Relationships)

Principles of Infectious Disease

Definitions

• Host - organism which provides nutrients, etc. to another organism
• Parasite - organism which lives at the expense of (and may even harm) its host; the parasite is generally smaller than the host and is metabolically dependent upon it
• Disease - an upset in the homeostasis of the host, resulting in generation of observable changes
  • symptom - subjective evidence of damage to the host (headache, anorexia)
  • sign - objective evidence of damage to the host (fever, rash, vomiting)
• Infectious disease - one in which detrimental changes in health of the host occur as a result of damage caused by a parasite
• Pathogen - microorganism that is capable of causing disease
• Virulence - a measure of pathogenicity, which is the ability to cause disease
  • Virulent - microorganisms that readily cause disease (only small numbers of the microorganism are required to initiate and sustain infection)
  • Opportunistic - microorganisms that may or may not cause disease generally colonize, but do not infect, the host when usually found associated with a host, called normal microbiota, can cause disease if they are inadvertently introduced into a site where they do not usually reside, especially inside host tissues
  • Avirulent - microorganisms that do not cause disease
  • Attenuated - microorganisms with reduced ability to cause disease

Koch's Postulates

If a microorganism is the causative (etiologic) agent of an infectious disease, it must be:

• Present in every case of the disease, but absent from the healthy host
• Isolated and grown in pure culture
• Able to Cause the disease when a pure culture is inoculated into a healthy host
• Re-isolated from the host that was inoculated with the pure culture 

Steps in Pathogenesis

To cause disease, a pathogen must:

• Contact the host - be transmissible
• Colonize the host - adhere to and grow or multiply on host surfaces
• Infect the host - proliferate in host cells or tissues
• Evade the host defense system - by avoiding contact that will damage it
• Damage host tissues - by physical (mechanical) or chemical means 

Virulence Factors

Factors responsible for the virulence of a microorganism because they influence its ability to cause disease by affecting its invasiveness and/or its toxigenicity

• Adhesins - promote attachment to host cells and tissues
  • pili - Escherichia coli and Neisseria gonorrhoeae use these to attach to urethral cells; Salmonella and Escherichia coli uses them to attach to intestinal cells
  • capsules - Escherichia coli uses these for attachment to intestinal cells
  • type III secretion system - Escherichia coli uses this to aid attachment to intestinal cells ... check out part 1 of this E. coli animation to see how the type III secretion (injector) system is used to facilitate this process (be sure to click on the "Learn More" link that goes with it to do just that!)
  • hemagglutinins - bacteria (Salmonella and Bordetella) and many viruses use these to attach to various host cells
  • spikes (peplomers) - used by viruses to attach to cells they then infect
• Invasins - promote entrance into and/or movement through tissues or cells
  • fibrinolysin - enzyme produced by Staphylococcus aureus and Streptococcus pyogenes that dissolves blood clots, thus preventing bacterial isolation and promoting spreading
  • hyaluronidase - enzyme produced by bacteria like Staphylococcus aureus and Streptococcus pyogenes that digests connective tissue, allowing them to spread through tissues more readily
  • hemolysins - enzymes produced by bacteria like Clostridium perfringens and Staphylococcus aureus that dissolve red blood cells, causing anemia and limiting oxygen delivery to infected tissues
  • type III secretion system - Salmonella uses this to invade intestinal cells ... check out part 1 of this Salmonella animation to see how the type III secretion (injector) system is used to induce phagocytosis by host cells (be sure to click on the "Learn More" link that goes with it to do just that!)
  • hyphal extension - fungi (Aspergillis, Candida, Stachybotrys) can invade the tissues by growing hyphal elements into them
• Evasins - protect pathogen from host defense factors, especially phagocytes
  • capsules - bacteria like Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae use these to avoid phagocytosis ... here's how phagocytosis is supposed to work (movies courtesy of ASM MicrobeLibrary,Author: James A. Sullivan, CellsAlive! Video, Charlottesville, Virginia 22903 USA)
  • catalase - enzyme produced by Staphylococcus aureus and other bacteria to degrade peroxides, thus promoting survival inside phagocytes
  • coagulase - enzyme produced by Staphylococcus aureus and Yersinia pestis that promotes blood clotting (coagulation), thereby walling-off the site of infection and protecting these bacteria from phagocytosis; this also causes the characteristic appearance of the skin in black plague
  • M protein - this surface protein is produced by Streptococcus pyogenes to inhibit surface complement activation (which would cause opsonization)
  • leukocidins - Staphylococcus aureus, Streptococcus pyogenes and other bacteria use these to kill phagocytes by damaging their membranes
  • anti-phagosomal factors - various factors allow protozoans such as Leishmania and bacteria such as Chlamydia, Listeria, Mycobacterium, Rickettsia, and Salmonella to survive within phagocytes ... check out part 2 of this Salmonella animation to see how Salmonella does this (be sure to click on the "Learn More" link that goes with it to do just that!)
  • immune system blockades - viruses and some bacteria can produce (or trigger the host cell to produce) molecules that shut down the immune response to the parasite
• Toxins - this is a general category that includes any molecule that can promote damage to the cells or tissues of the host
  • exotoxins - toxic proteins that are secreted by living microbes
    • botulin - Clostridium botulinum neurotoxin causes flaccid paralysis in botulism
    • tetanospasmin - Clostridium tetani neurotoxin causes simultaneous contraction of opposing muscles, resulting in tetany, which is painful and makes tetanus a life-threatening disease
    • enterotoxin - Escherichia coli, Staphylococcus aureus, Vibrio cholerae and other bacteria produce this toxin, which causes intestinal cells to pump water and salts (electrolytes) from the bloodstream into the intestine, causing diarrhea that leads to dehydration, shock, and even death in the worst cases
    • diphtheria toxin - Corynebacterium diphtheriae produces this exotoxin, which damages cells of the heart, kidneys and central nervous system by inhibiting protein synthesis, thus resulting in diphtheria
    • gliotoxin this exotoxin causes the bright red inflammation seen in Candida infections
  • endotoxin - lipopolysaccharide (LPS) portion of the outer membrane of Gram-negative bacterial cell walls which is released when the bacteria disintegrate and causes fever and/or endotoxin shock, depending on its concentration in the bloodstream