Notes 12/7


November 30, 2009

Host-Pathogen Interactions

- Cannot grow viruses on a pure culture agar – MUST grow them in a host cell
- Cell Culture:
o If we need to grow a virus that ONLY infects humans – use cell culture
• Cells are placed in a flask or a dish
o Humans cancer cells are used because they divide indefinitely – whereas normal cells commit suicide after about 30 replications
o Still need to be provided with nutrients
• Cells are placed across the bottom
• Nutrient-rich fluid (similar to blood plasma) is them put in
o Common cultured cancer cells = HeLa cells
• Named from a person who died of her cervical cancer
• Henrietta Lacks infected with HPV-18
• HPV-18 destroys apoptosis (cell suicide) mechanism in epithelial cells → this made infected cells cancerous
o Cancer cells in general have large nuclei and are continually misshapen

Questions to Consider:
• How do pathogens and hosts influence each other’s evolution?
• How does ecology contribute to the ability of pathogens to cause disease?
• Do pathogens inevitably evolve to become less virulent to their hosts?
• Why do bacteria make ‘toxins’?
• What is the difference between a pathogen and normal flora

I. Terminology
a. Incidence vs. prevalence
i. Incidence
1. The number of new cases of a disease in a population divided by the total number of people in population
ii. Prevalence
1. Total number of cases of a disease divided by the total number of people in the population
b. Epidemic
i. Increase in incidence of a disease
c. Reservoir
i. Where the organism that causes the diseases habitually exists in nature
1. Ex. – HIV’s reservoir is in humans
2. Ex. – C. perfringen’s reservoir is soil
3. Ex. – V. fischeri’s reservoir is squid, seawater
ii. Microbes tend to become less virulent in their reservoir
d. Vector
i. Organism that transmits infectious diseases from host to host
1. Ex. Y. pestis (black plague) vector = flea
e. Virulent
i. Microbe that causes symptoms
f. Virulence
i. Ability to cause disease symptoms in a host
g. Virulence factor
i. Any chemical made by a pathogenic microbe that contributes to that microbe’s ability to cause symptoms
h. Invasive disease
i. Any infectious disease where the problems are caused by microorganisms living in what normally, in a healthy person, is a sterile sight
1. Ex. Heart, Blood, Muscle, CSF
ii. Invasion factors
1. Chemicals produced by pathogens that allow those pathogens to get into normally sterile tissue
i. Toxigenic disease
i. Disease caused by microorganisms growing in a normally non-sterile site, producing “toxin” that → symptoms in a host
1. Ex. S. aureus makes TSST-1
ii. Exotoxin
1. Protein that is expressed by actively growing bacteria → symptoms in a host
a. TSST-1
iii. Endotoxin = lipid A of LPS
1. Not secreted by actively growing bacteria – just part of gram (-) outer membrane, only being released if the bacteria dies
II. Two examples of toxigenic bacterial diseases
a. Botulism
i. Clostridium botulinum (like other clostridia sp.)
1. Strict anaerobes
2. Spore-forming
a. Spores – very sturdy, non-metabolic, suspended animation bacteria
b. When in a favorable environment they will germinate and grow – expressing the botulism toxic gene
3. Reservoir – Soil
ii. Botulism toxin
1. When Clostridium botulinum is actively growing it expresses botulism toxin
a. Protein that causes symptoms in us when we have it inside of us
2. Deadly dose: 1ng/kg weight of a person
3. Death from suffocation: BoTox disables motor neurons, including those that control diaphragm → can’t breathe
iii. Botulism food poisoning
1. In home canned foods – Used to – have stray botulism spores on the vegetables. The prepping of the food would take all of the oxygen out of the can creating an anaerobic environment – allowing for germination of botulism spores (grow into active bacteria)
a. When they grow actively they express the botulism toxin protein – most toxic substance known to man-kind
2. Don’t have to ingest the bacteria to get sick – just ingesting the toxin is enough
iv. Infant botulism and normal flora
1. Human body has lots of normally non-sterile sights that are anaerobic
a. Ex. Gut
2. C. botulinum spores in soil and many other places
3. Normal flora in the gut prevent the botulism spores from having anywhere to grow – they will just pass out of your system after they are eaten AS SPORES
a. The spaces that would be a good place for them to grow are already filled up with normal flora
4. In infants there is little normal flora to displace the bacteria – thus the bacteria grow and harm the baby greatly – baby can’t hold its own muscles up anymore ‘floppy-baby syndrome’
v. Why does C. botulinum produce botulism toxin?
1. Reservoir = soil
2. Since reservoir is soil, almost certainly botulism toxin for improving bacterial survival in soil, NOT for killing people
b. Cholera
i. John Snow – Broken pump handle epidemic
ii. Vibrio cholerae
1. Gram (-) rod that can live in salt or freshwater
2. Sensitive to acid – so you have to ingest >1,000,000 in one shot in order to get sick
a. 1st world countries don’t have very many problems because we have very clean water and ingesting that much cholera at one time is not very likely at all – 3rd world countries and such, however, it is quite likely that this will occur
3. When growing, produces cholera toxin
iii. Cholera symptoms
1. Lots (>2 gallons/day) of watery diarrhea
a. Leading cause of death in the world for children is diarrhea
iv. Cholera toxin
1. Makes epithelial cells pump NaCl out, because of osmosis, water follows
2. Makes copepods healthy
v. Cystic fibrosis
1. Super sticky mucus in lungs because can’t ship NaCl out of the epithelial cells – meaning they can’t ship very much water out either
a. Same amount of mucus as everyone else, just a lot more dense and harder to clear
2. If you have cholera, having cystic fibrosis is good because you won’t have the massive amounts of diarrhea that will kill you through dehydration
3. Heterozygote advantage
a. People who have 1 CF allele and 1 normal allele, are protected against cholera as well, BUT they do not have cystic fibrosis either
vi. Copepods
1. Tiny arthropods that live in salt water and travel to freshwater
2. Reservoir for cholera
3. V. cholera = necessary normal flora for copepods
a. Copepods would die without cholera toxin
III. One example of invasive bacterial diseases
a. Scarlet fever
i. Streptococcus pyogenes
1. Gram (+) streptococci → “Strep throat”
2. Very vivid bright red rash all over the person’s trunk, swollen bright red strawberry tongue, pussy things on the back of the throat
3. Invades normally sterile body parts
4. Used to cause scarlet fever, have not gone away, just don’t cause scarlet fever anymore
a. When it was scarlet fever, VERY aggressive quarantine measures taken – would not see ANYONE else except a doctor (priest before death)
b. IF the child got better every single thing that the child touched while he was sick was burned so no one else would catch the disease
c. Thus, could no longer afford to make toxins for it
d. Aggressive quarantine measure changed the evolution of S. pyogenes such that it lost most of its virulence factors that caused most of the scarlet fever symptoms
ii. Virulence factors
iii. Strep throat and flesh-eating bacteria
iv. Whatever happened to scarlet fever?
IV. Ewald’s hypothesis
a. Over time all pathogenic microbes evolve towards reduced virulence to its host – over a time scale virtually all pathogens turn into normal flora

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