Tortora Chapter 15

1
Tortora Chapter 15

• Microbial Mechanisms of Pathogenicity

2
Some terms

• Pathogenicity-ability to cause disease
• Virulence-degree of pathogenicity (how bad is it?)

3
Entering the host-portal of entry

• 1. skin-intact skin is first line of defense
• some bacteria can enter thorough hair follicle
  or sweat gland
• some bore through skin (remember which parasite
  does this?)
• 2. mucous membrane-penetrate the membrane lining
  the respiratory, digestive, genitourinary tracts
  or the conjunctiva of eye

4
Portal of entry continued

• 3. Parenteral route-punctures, bites,
  injections, cuts, wounds, surgery, splitting due
  to dryness or swelling
• Examples include HIV, hepatitis, Clostridium
  tetani and Clostridium perfringens

5
Preferred portal of entry

• Many bacteria MUST enter through a particular
  portal or they cant cause infection or disease
• Salmonella typhi must enter through digestive
  system. If it is rubbed on skin it wont cause
  the disease
• Some can cause problems in more than one portal
• Anthrax may enter thorough digestive, pulmonary,
  or skin (see web site for pictures)
  http//www.bt.cdc.gov/agent/anthrax/anthrax-images
  /cutaneous.asp

6
Number of microbes

• The virulence of a microbe is expressed as its ID
  50 or infectious dose for 50 of the sample
  population
• This varies depending on the bacteria
• ID for anthrax obtained by cutaneous route is
  10-50 endospores
• ID for inhaling anthrax spores is 10,000- 20,000
• ID for gastrointestinal is 250,000-1,000,000
• Potency of toxin is express as LD 50 (lethal dose)

7
Adherence

• Once inside the bacteria must stick to host
  tissue
• Often have adhesions or ligands to help with this
• These bind to specific receptors on cells of host
  tissue

8
Penetration of host defenses

• 1. capsules-Streptococcus pneumoniae, Klebsiella
  pneumoniae, Haemophilus influenzae all have
  capsules that are related to virulence.
• 2. Cell wall components-
• M protein in Streptococcus pyogenes is heat and
  acid resistant
• fimbriae help with attachment
• mycolic acid in Mycobacterium tuberculosis

9
Penetration continued

• 3. Enzymes-extracellular enzymes can digest
  materials, digest blood clots, etc
• Coagulase-clot fibrinogen in blood (staph)
• Kinase-digest clots (streptokinase and
  staphylokinase)
• Hyaluronidase (spreading factor)-helps
  microorganism spread from initial site of
  infection (streptococci)
• Collagenase-breaks down collagen (Clostridium)
• IgA protease-destroy the antibody IgA (N.
  gonorrhoeae)

10
Penetration continued

• 4. antigenic variation-some pathogens alter
  there surface antigens so that antibody doesnt
  recognize or affect them
• 5. penetration into cell cytoskeleton-some
  microbes produce invasins that rearrange actin
  filaments in cytoskeleton and cause membrane
  ruffling allowing the microbe to sink in and by
  engulfed by the cell

11
Damage to host cell

• 1. using host nutrients-some pathogens secrete
  siderophores to take iron away from host
• 2. direct damage-cells often rupture when
  bacteria metabolize inside and pathogens spread
  to other cells (E. coli, Shigella, Salmonella)
• 3. toxins-poisonous substances that are often the
  primary factor!

12
More on Toxins

• -toxigenicity-the ability to produce toxins
• Toxemia-presence of toxins in blood
• Intoxication-ingesting a toxin
• Antitoxins-antibodies produced to provide
  immunity to toxins
• Toxoids-toxins that have been altered to
  stimulate antitoxins

13
Exotoxins

• produced inside some bacteria as part of growth
  and metabolism and are usually secreted (gram
  positive typically)
• These are among the MOST lethal substances known
  to man!
• Neurotoxins-attack nerve cells
• Cardiotoxins-attack heart cells
• Hepatotoxins-attack liver cells
• Leukotoxins-attack white blood cells
• Diptheria toxin and tetanus toxin-named for the
  disease

14
Membrane disrupting toxins

• Leukocidins-form protein channels and kill white
  blood cells
• Hemolysins-form protein channels and kill red
  blood cells (streptolysin O and stroptolysin S)
• O is for inactivated by oxygen and S is for
  stable in oxygen

15
Superantigens

• Antigens that provoke intense immune response
• They are bacterial proteins that stimulate T
  cells to produce cytokinins
• Cytokinins in high levels also cause symptoms
  like fever, nausea, vomiting, diarrhea, and may
  cause shock and death

16
Some types of exotoxins

• Diptheria toxin- Corynebacterium diptheriae
  produced this ONLY when it is infected by a phage
  (bacteriophage)
• Erythrogenic toxin- Streptococcus pyogenes these
  superantigens that destroy the plasma membrane of
  capillaries and produce a red rash (scarlet
  fever)
• Botulinum toxic (botox)-produced by Clostridium
  botulinum is THE MOST TOXIC, it is a neurotoxin
  that affects the neuromuscular junction and
  prevents transmission (flaccid paralysis)

17
More exotoxins

• Tetanus toxin- Clostridium tetani produces the
  tetanospasmin, also a neurotoxin, but it reacts
  by inhibiting the release of Acetylcholine from
  the neuromuscular junction (spastic paralysis)
• Vibrio enterotoxin-produces cholera toxin that
  causes large amounts of fluid loss, severe
  diarrhea, and vomiting
• Staphylococcal enterotoxin- this superantigen
  causes disruption in intestinal wall similar to
  vibrio leading to diarrhea and vomiting

18
Endotoxins

• These are part of the outer portion of the cell
  wall of gram negative bacteria
• This outer membrane has a component called
  lipopolysaccharide (LPS) that contains Lipid A
  (THE TOXIN)
• Endotoxins are released when the gram negative
  dies
• The are also released when the bacteria undergoes
  multiplication

19
Effects of endotoxins

• The release of endotoxin stimulates macrophages
  to release cytokines in high concentration (which
  are toxic at high levels)
• It also causes chills, fever, weakness, aches,
  maybe shock and death (endotoxin shock)
• Endotoxins can cause miscarriage (spontaneous
  abortion)
• Endotoxin may also cause blood clots which can
  cause the death of tissues (disseminated
  intravascular clotting)

20
Endotoxin and fever

• Fever is called pyrogenic response
• Endotoxins cause macrophages to produce
  interleukin-1 (IL-1)
• This is carried in the blood to the hypothalamus
  which controls temperature
• IL-1 causes the hypothalamus to release
  prostaglandins which reset the temperature higher
• Aspirin and acetaminophen reduce fever by
  inhibiting the release of prostaglandin

21
Shock

• Any life threatening decrease in blood pressure
• Shock caused by bacteria is called septic shock
• Gram negative bacteria cause endotoxin shock
• When phagocytes ingest bacteria the phagocytes
  release tumor necrosis factor (TNF)
• TNF causes damage to capillaries, causing fluid
  loss and a drop in BP.
• http//www.whale.to/v/reisinger3.html for an
  interesting article on shock

22
Comparison of exo and endotoxin

• Consult table 15.3
• AND/OR
• http//www.life.umd.edu/classroom/bsci424/HostPara
  siteInteractions/ExovsEndo.htm