week 11 - bacteria disease

Question 1

bacteria in disease:
virulence factors

Answer 1

• Virulence factors: characteristics of the microorganism that allow it to cause disease
  o Colonisation of the host
  o Avoidance of the immune response
  o Acquisition of nutrients
  o Damage to the host
  o dispersal

Question 2

Mycobacterium tuberculosis (Mtb)
overview

Answer 2

• Obligate aerobe
• Facultative intracellular parasite
  o Can live within macrophages (white blood cells)
• Slow growing: division time 16-20h
  o So doesn’t trigger a large immune response
• Acid-fast
  o Mycolic acids on the cell surface create a hydrophobic layer
  o So cannot stain with gram stain as layer repels it
• Complex cell wall
  o Virulence factor
  o Contributes to antibiotic resistance

Question 3

Tuberculosis (TB)

Answer 3

• M. tuberculosis causes Tuberculosis (TB)
  o Usually an infection of the lungs
  o Can affect other organs
• Leading cause of death due to a single infectious agent in 2016
  o ~1.5 million deaths per year
  o 1/3 of world population infected
   Carriers, don’t show symptoms
  o Common opportunistic infection in people with HIV/AIDS

Question 4

Tuberculosis (TB)
primary infection

Answer 4

• Primary infection
  o Droplets containing Mtb are inhaled
  o Mtb taken in by macrophage
   Survive and grown in macrophage
  o Granulomas form in lungs
   Organised immunological structure contained many immune cells, lasts a long time, fuses with epithelium of lung, Tb let out, cough, droplets spread
  o Cavitation of granulomas releases Mtb into the lung and results in transmission through coughing

Question 5

Tuberculosis (TB)
post primary infection

Answer 5

• Most individuals are asymptomatic
  o Do not develop acute disease
  o Cell mediated immune response is protective and life long
  o Hypersensised and protected against further infection
• Some patients develop post-primary TB
  o Reinfection with dormant mTb
  o Immunosuppression
  o HIV/AIDS

Question 6

Mycobacterium tuberculosis:
virulence factors

Answer 6

• Thick complex lipid-rich cell walls  cell wall impenetrable, difficult for immune cells and antibiotics to puncture and destroy

Question 7

Mycobacterial cell wall:

Answer 7

see notes

Question 8

Mycobacterium tuberculosis:
virulence factors
growth

Answer 8

• Grows very slowly, causes chronic infections

Question 9

Mycobacterium tuberculosis:
virulence factors
- intracellular pathogen

Answer 9

o Survives and replicated inside macrophage
o Arrests phagosome maturation and limits acidification
o Protected from antibodies
o Access to nutrients

Question 10

multi-drug resistant TB

Answer 10

• Resistant to the most effective drugs against TB
  o i.e. rifampicin and isoniazid
• worldwide 4.6% of patients with TB have a MDR TB
• in some countries the rate is 25%
• XDR TB also is resistant to second line druge
  Very difficult to treat
  Antibiotics different mechanism of action
• Use to that tackle different parts of cell
• But because multiresistant this doesn’t work for Tb

Question 11

TB diagnosis and treatment

Answer 11

• Multidrug regimens used
  o Prevent the emergence of resistance during therapy and more effective
  o Treatment over many months
• Drugs specific to TB
  o First line: Isoniazid and Rifampicin
  o Second line: Streptomycin, Ethambutol, Ryazinaminde
• Diagnosis is difficult
  o Slow growin
  o Symptoms slow to show
  o Important to prevent transmission
• PCR to detect Tb
  o ambiguous

Question 12

Helicobacter pylori

Answer 12

• Gram-negative, highly motile, spiral-shaped bacterium
• Microaerophilic
  o Require O2 at lower than atmospheric concentrations (3-15%)
• Associated with gastritis (infection of stomach lining)
  o Gastric ulcers, gastric cancers
• Colonizes gastric epithelium
• Orally transmitted person-to-person
  o in families?

Question 13

Link between H. pylori and peptic ulcers

Answer 13

• conventional thinking
  o bacterium cant live in human stomach (pH1)
  o peptic ulcers caused by stress
• seen in 1979 by Australian pathologist Robin Warren in Perth, Australia
• unable to grow it
  o unintentionally left their plates incubating for 5 days over easter weekend 1982
  o initial skepticism: association may not by causal
• 1985 marshall drank a beaker of H. pylori culture
  o Developed nausea and vomiting
  o Endoscopy confirmed gastritis and the presence of H. pylori
• Antibiotics
  o Effective in treatment of gastritis
  o Prevention of relapse of ulcers
• Warren and marshall
  o Rewrote textbooks with reference to what causes gastritis and peptic ulcers
  o Simple cheap antibiotic regime replaces tortuous surgery
  o In 2005 awarded Nobel Prize in Medicine

Question 14

H. pylori virulence factors

Answer 14

1. Flagella motility (polar flagella and spiral shape) and chemotaxis
   - Needed to reach mucosa (and burrow in )
2. Urease
   - Neutralised acid
   - Scavenges nitrogen
   - Ammonia damages mucosa
3. Toxins
   - CagA and VacA
4. Enzymes
   - Mucinase, proteases

Question 15

Neisseria gonorrhoeae

Answer 15

• Gram negative, cocci, obligate aerobe
• Sensitive to drying, sunlight, UV light
• Causes gonorrhea – STD
• Females
  o Mild vaginitis, can lead to pelvic inflammatory disease
• Males
  o Painful infection of urethral canal

Question 16

N. gonorrhoeae: virulence factors

Answer 16

• Type four pius
  o Adhesion to the urogenital tract
  o Twitching motility
   Attach to human cells
• Lipooligosaccharide (LOS)
  o LPS without the O polysaccharide
  o Triggers intense immune response (purulent discharge)
  o Microcapsule of sialylated LOS
  o Disguise from the host immine system
   Thinks its sialylated acid

Question 17

Treatment of gonorrhoea

Answer 17

• Antibiotics
  o Penicillins and cephalosporins (target peptidoglycan)
  o Resistance is now common