Host-Parasite Interaction 2

Question 1

the “opportunistic” pathogen

Answer 1

• Pseudomonas aureginosa

- biofilm formation in pathogens

Question 2

the commensal gone bad

Answer 2

• helicobacter pylori and hepaticas

- pathogenicity islands

Question 3

Pseudomonas aeruginosa

Answer 3

• only a pathogen in compromised hosts (burn victims and those with cystic fibrosis)
• accounts of 10% of hospital infections
• normally soil bacterium (very metabolically flexible)
• used as a bio-remediator.

Question 4

Characteristics of pseudomonas aeruginosa

Answer 4

• can grow on 75 other organic substrates and ammonium
• wide temperature range
• naturally resistant to antiseptic compounds and many antibiotics (LPS and EPS)
• forms biofilms
• possibly the most prevalent bacterium.

Question 5

Toxin

Answer 5

• Endotoxin (LPS)

- produces a large quantity of LPS used in biofilm formation.

Question 6

“mucoid” phenotype

Answer 6

• exopolysaccharide is made of alginate
• its expression is induced by environmental factors such as starvation and the alternative sigma factor.
• requires 25 alg genes to be produced, and is required for biofilm formation.
• typically the strains that cause human infection.

Question 7

biofilm

Answer 7

• physical barrier against chemical and immune responses.

Question 8

alginate composition

Answer 8

• composed of mannuronic acid and guluronic acid.

Question 9

Factors required for biofilm formation

Answer 9

• quorum sensing
• motility (both flagella and twitching)
• alginate production

Question 10

motility

Answer 10

• flagella bind to surface

- if they do not twitch and can’t move the biofilm is flat.

Question 11

quorum sensing

Answer 11

• use two homoserine lactones and a quinolone
• all are constitutively expressed
• only if intracellular concentration of any one reaches a critical level, biofilm formation is induced.

Question 12

steps in biofilm production

Answer 12

• alginate production is the first step in biofilm creation
• serves to secure the bacteria to the substrate and allow for the colony to grow vertically.
• channels in biofilm allow bacteria access to the nutrients in the medium.

Question 13

Pseudomonas and Cystic Fibrosis

Answer 13

• 80% of CF patients are infected with P. aeruginosa - will keep for life
• Infected patients have decreased pulmonary function and die sooner - lungs fill with mucus
• 80% of clinical isolates have acquired resistance
• Mucoid and biofilm production further makes eradication problematic

Question 14

Cystic Fibrosis Transmembrane conductive regulator

Answer 14

• have mutations in the protein CFTR
• CFTR is a membrane ABC transporter and chloride channel that controls concentration of chloride ion found near mucosal surfaces

Question 15

Result

Answer 15

• chloride imbalance in skin and mucosal surfaces affects viscosity of mucus covering the lung epithelia, making it harder to clear out bacteria.
• ciliary flow is disrupted in CF lungs which make it easier for biofilm formation.
• CF lungs are susceptible to many types of infection.

Question 16

Symptoms of CF after Pseudomonas infection

Answer 16

• increased frequency, duration, and intensity of cough
• increased or new onset of sputum production and appearance
• increased shortness of breath and decreased exercise tolerance
• decrease in overall well-being, increased fatigue, weakness, fever, poor appetite

Question 17

physical signs of CF after Pseudomonas infection

Answer 17

• increased work of breathing. intercostal retractions and use of accessory muscles
• increased respiratory rate
• increased air trapping
• fever
• weight loss

Question 18

Helicobacter pylori

Answer 18

• only lives in humans.
• about 50% of all people on earth are infected with it, but was probably higher in the past.
• first described in 1983 by Marshall and Warren

Question 19

Marshall and Warren

Answer 19

• noticed patients with gastric ulcers tended to have what looked to be bacteria in the stomach lining
• stomach was thought to be a sterile environment due to acidic pH and digestive enzymes.
• Marshall used Koch’s postulates on himself

Question 20

Epidemiology

Answer 20

• after infection most people will come down with chronic superficial gastritis - upset stomach
• a small percentage will develop gastric ulcers many years later
• if kept for decades, the person has a high risk for certain types of gastric cancer.
• researchers detected it in blood dating back 50 years

Question 21

Urease

Answer 21

• H. pylori doesn’t like an acidic pH and will burrow down into the stomach
• to combat stomach acid, it will produce large amounts of urease

Question 22

urease mechanism

Answer 22

• splits urea into CO2 and ammonia.

- ammonia will neutralize the acid but will also degrade the stomach lining causing the ulcer.

Question 23

detection

Answer 23

• will be given urea with radioactively labeled carbon

- patients breath is taken and analyzed for presence of labeled CO2

Question 24

Cag pathogenicity island

Answer 24

• Cag status is correlated with more severe pathologies, but is not required for colonization or persistence
• encodes a type four secretion system
• CagA is the delivered effector molecule
• CagA is phosphorylates by the host Src kinase, which causes actin rearrangement of epithelial cells
• induces IL-8 cytokines.

Question 25

Helicobacter hepaticus

Answer 25

• certain strains of mice were developing liver cancer at an unusual frequency
• associated with enterocolitis and cancer
• lives in small intestine

Question 26

Cag postive strains

Answer 26

• typically more pathogenic than those that do not have the island.

Question 27

evidence of recent acquisition

Answer 27

• different G+C codon bias

- strains are either completely + or -

Question 28

How to recognize an Island?

Answer 28

• have a difference % G/C DNA content from the rest of the DNA
• have a different “codon bias” from the rest of the genes
• Are in the middle of a gene/operon where it doesn’t belong
• Are present in some members of a species, absent in others.
• type III and IV secretion systems are sometimes found on islands.

Question 29

Cag

Answer 29

• CagA is phosphorylated by the host Src kinase, which causes actin rearrangement of epithelial cells
• Cag is not required for colonization or persistence in the stomach.

Question 30

codon bias

Answer 30

• bacteria tend to use the same triplet to encode an amino acids, even though the codon is redundant.

Question 31

hummingbird phenotype

Answer 31

• actin polymerizes off the ends and looks like a hummingbird’s beak

Question 32

H. pylori and esophageal cancer

Answer 32

• if you have H. pylori, you will be less likely to get esophageal cancer.

Question 33

The HHGI1 Pathogenicity Island

Answer 33

• found in helicobacter hepaticus

- mice with pathogenicity island (+) strains are more likely to have liver infections.

Question 34

Gram secretion systems

Answer 34

• analogous to type IV
• deliver a molecule directly across membrane into host.
• host cells with type IV mutants have dramatically different transcription profiles.
  
  • transcribe a lot less

Question 35

Type VI

Answer 35

• makes easier to bacteria and immune system to live together