Mycobacteria Flashcards
What species cause infection?
M. tuberculosis - causes tuberculosis in humans - TB = tubercle bacilli - humans are the only konwn resevoir M. bovis - Cuases tuberculosis in cows - Humans can be infected by drinking unpasteurized milk M. avium - Can cause a tuberculosis-like illness in humans, particularly in AIDS patients M. leprae - causative agent of leprosy in humans
True or false?
Tuberculosis is the 2nd leading cause of death after AIDS
True
Who was M. tuberculosis isolated by?
Robert Koch in 1882
General info on M. tuberculosis
Obligate human pathogen, intracellular pathogen, Non-motile, rod shaped, obligate aerobe
- can be grown, but takes 4-6 weeks to get small colonies (generation time >15h)
Mycobacteria have high [mycolic acid] in the cell envelope, what is the significance of this?
- Resistance to many antibiotics
- resistance to killing by acidic and alkaline compounds
- Resistance to osmotic lysis via complement deposition
- Resistance to lethal xidative stress and promotes survival inside of macrophages
- Impermeability to stains and dyes
- Acid fast (resists common stains)
What is an acid fast stain?
- Stained with the basic dye carbol-fuchsin with slow heating (to melt wax)
- Washed with EtOH and HCL
- Counterstained with methylene blue
- Acid-fast organisms appear red, whereas non-acid fast organisms appear blue
What is Stage 1 of tuberculosis?
- transmission from inhalation of droplets from an infected host (coughing/sneezing)
- can generate 3000 droplet nuclei (can contain 3 bacteria)
- small droplets can stay airborne for a while and inhaled directly into lungs
What is stage 2 of tuberculosis?
- 7 - 21 days after initial exposure
- alveolar macrophages phagocytize TB cells
- TB can multiply in unactivated macrophages
- Macrophages will lyse and release TB cells to infect more macrphages
What is stage 3 of tuberculosis?
- infected macrophages form granulomas - TB inhibits fusion of phagosome with lysosome to survive and grow in the macrophage
What are granulomas?
- Tubercles of immune cells trying to destroy invading pathogens
- Represents a balance between the pathogen and host (latent infection)
- Macrophages at the centre are harder to activate by T cells
- activated macrophages can kill TB and present to T cells
- Macrophages cause caseous necrosis and dead cells maintain a cheese like appearance
What is stage 4 of tuberculosis?
- Some macrophages remain infected
- Tubercle grows, erosion of granuloma in airway provides the route of transmission (cough)
- Deterioration of host immunity can result in a life threatening infection (active TB)
- Caseous centre can liquefy leading to cavitation (hole/cavity in lung)
What is the difference between pulmonary and extra pulmonary TB?
Pulmonary = contagious (75%)
- Progressive, irreversible lung destruction can occur and bacteria may enter bloodstream
- Latent carriers do not transmit the infection (single inhaled bacteria can infect though)
Extra pulmonary = non-contagious (25%)
- more likely to occur in immunocompromised individuals
- can infect: bone, joints, liver, spleen, GI tract and brain
- Systemic spread can cause miliary TB (fatal)
What % of infected people develop disease?
10%
Symptoms = long cough with thick and possibly bloody mucus, fever, chills, fatigue, weight loss, chest pain, shortness of breath, pallor (pale skin, white death)
What are symptoms of Extra pulmonary TB?
They can vary depending on where TB spread to
What is the testing and diagnosis for TB?
TB test = PPD (purified protein derivative)
- a person is infected if they convert from negative to positive on a TB skin test
- positive = red, swollen circle at 48h
- delayed-type hypersensitivity
What do negative and positive results for the TB test mean?
Negative = not infected, immune compromised or not infected long enough Positive = Latent or active TB or BCG vaccinated (chest x-ray for upper lobe "shadowing" = lesions)
How deadly is TB if untreated?
will kill 2/3 people
What is the treatment for TB?
6 months of antibiotics for the short treatment (slow growth = long treatments)
Multiple Antibiotics:
- Rifampin (inhibits RNA polymerase)
- Isonazid (inhibits mycolic acid synthesis)
Why give 2 or more drugs?
10^11 bacteria possible in tubercle (hube amount)
- minimizes development of resistance (has to develop 2 of them)
What is the difference between MDR-TB and XDR-TB?
multi-drug resistant TB = MDR-TB
- resistant to the first 2 most effective first-line therapeutic drugs, isoniazid and rifampin
Extensively-drug resistant TB = XDR-TB
- Also resistant to the most effective 2nd-line therapeutic drugs used commonly to treat MDR-TB
- XDR-TB has been found globally and can be untreatable
What is BCG and why does it result in a false positive on the TB test?
Bacille Calmette-Guerin
- living vaccine prepared from attenuated M. bovis which shares antigenicity with TB
- controversial du to variable efficacy (~80% or more)
- leaves large scars (only recommneded if at high risk of exposure)
Which is more widely spread HIV/AIDS or TB?
People living with HIV = 33.3 million
People living with TB = 2 billion people
What is leprosy?
Chronic diesase caused by M. leprae (Hansen’s disease)
- slow growth (incubation period ~5 years)
- Causes permanent damage to skin, nerves, limbs and eyes
- rare in developed countries
- 2 million people are permanently disabled bny leprosy (mainly tropical developing countries)
What does M. leprae share with M. tuberculosis?
Both are Gram+ acid fast, rod shaped, aerobic and have waxy cell envelopes (mycolic acid)
Where can M. leprae grow?
- foot pads of mice (low #s)
- Systemic infection in armadillp (10^10 per gram of infected tissue)
- M. leprae infects macrophages of skin and schwann cells in nerves
What is more infectious TB or leprosy?
Leprosy is much less infectious
- Despite this victims of leprosy have been ostracized (killed, rejected by family, etc.)
- This may be because lesions in TB are hidden, but in leprosy they are visible
What are the 2 major forms of leprosy and what % of people will develop the disease?
Tuberculoid and lepromatous
- 95% will not develop disease
What is Tuberculoid Leprosy?
- cell-mediated immunity present
- macrophage can contain the bacteria
- lesions with “anesthetic” areas
- loss of hair and pigmentation
- tuberculin positive
- bacterial cells are not recoverable from lesions
- can be self limiting
What is Lepromatous leprosy?
- Cell-mediated immune responses are absent
- Macrophages are not activated
- M. leprae survives and multiplies in macrophages and Schwann cells
- damges nerves = loss of sensation leads to inadvertant traumatic lesions
- Can cause loss of eyebrows, thickening and enlarged nares, ears and cheeks (lion-like appearance)
- lesions can become secondarioly infected resulting in disfigurements and mutilation
What is the spread and progression of leprosy?
- Transmission is not well understood
- Close (direct) contact for long time periods is hypothesized
- most exposed individuals do not develop disease (host genetics may be important)
Is leprosy treatable, and how if so?
- Yes, with multiple antibiotics for 6 months to a year
- Dapsone (1940) used until resistance developed (1960s)
- In 1980 MDT - dapsone, rifampin, clofazimine
- After one does of MDT (multi-drug therapy) patients no longer transmit the disease
Is Leprosy still stigmatized today?
Yes, people are still very fearful of the disease due to the appearance of victims
