13. Legionella & TB Flashcards

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1
Q

What bacterium causes Legionnaire’s disease?

A

Legionella pneumophila

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2
Q

How does Legionella pneumophila cause Legionnaire’s disease?

A

Evasion of destruction by phagosome

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3
Q

Legionella only grow?

A

Intracellularly in macrophages - do not grow on agar plates

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4
Q

A non-pneumonic variant caused by the same species as Legionella pneumophila is called?

A

Pontiac fever

Non-pneumonic - found other places besides the lungs

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5
Q

Features of Legionella species?

A
  • Poorly staining
  • Obligate (needs cells to replicate in)
  • Aerobic
  • Gram negative bacilli
  • Tricky to culture, visualise & stain
  • Rod-shaped
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6
Q

Is L. pneumophila spore-forming?

A

No

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7
Q

Symptoms of Legionnaire’s disease?

A

Initial symptoms within 2-10 days may include loss of energy, headache, nausea, aching muscles, high fever & chest pains.
Victims who survive may suffer permanent physical or mental impairment (20% fatality rate)

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8
Q

Has person-person spread of Legionnaire’s disease ever been demonstrated?

A

No

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9
Q

Death rate of those identified with Legionnaire’s?

A

20%

10,000 - 100,000 cases in US

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10
Q

How is Legionnaire’s contracted?

A

By inhaling airborne water droplets containing Legionellae

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11
Q

Legionnaire’s disease is particularly associated with?

A

Man made things e.g cooling water used in air conditioning

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12
Q

Where does infection by Legionella begin in the body?

A

Lower respiratory tract

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13
Q

Legionnaire’s disease pathogenesis:

A
  • Bacteria bind alveolar macrophages via complement receptors & are engulfed into a phagosomal vacuole
  • T4SS stimulates the uptake of bacteria into the macrophage
  • Bacteria block fusion of lysosomes with phagosome, preventing normal acidification of phagolysosome
  • Bacilli multiply within phagosome (which becomes a Legionella-containing vesicle)
  • Phagosome modified to become a privileged niche for bacteria to replicate
  • Eventually, the cell is destroyed, releasing a new generation of microbes to infect other cells
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14
Q

Why is infection by Legionella difficult to diagnose?

A

Because they only grow inside macrophages

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15
Q

What happens if phagocytosis is prevented by treatment with cytochalasin?

A

The bacteria (Legionella) are denied access to the intracellular environment and growth does not occur

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16
Q

True or False: Legionella do not replicate in water but can infect amoeba and multiply

A

True

Amoeba are a training ground for intracellular bacteria.

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17
Q

What are the most important virulence factors in Legionella?

A

Those that help modify the phagosome

18
Q

What does Legionella use to secrete proteins into the phagosome itself?

A

Type 4 Secretion System

19
Q

What is the most important virulence factor in Legionella pnuemophila?

A

Dot/Icm T4SS

Dot = defect in organelle trafficking, Icm = intracellular multiplication

20
Q

What gene has been shown to have some role in adhesion, invasion and phagosome trafficking in macrophages and amoeba?

A

RtxA gene

21
Q

What has pore-forming activity and is required for bacterial egress from mammalian or protozoan cells after bacterial replication is complete?

A

IcmT

22
Q

Different strains of Legionella have different…

A

effector profiles

23
Q

The symptoms of Legionella infection undoubtedly result from a combination of what?

A
  1. Physical interference with oxygenation of blood
  2. Ventilation-perfusion imbalance in the remaining lung tissue, and
  3. Release of toxic products from bacteria & inflammatory cells
24
Q

What greatly reduces the death rate of Legionnaire’s?

A

Prompt treatment with erythromycin

25
Q

Are there vaccines available for Legionnaire’s disease?

A

No

26
Q

What 3 bacteria undergo phagosome modification (central part of virulence strategy)?

A
  1. S. typhimurium - T3SS effector proteins secreted to block phagosome maturation resulting in the formation of SCV (salmonella containing vacuole) formation
  2. L. pneumoophila - T4SS effector proteins secreted to prevent fusion of LCV (legionella containing vacuole) with endolysosomal compartments, and promotes fusion with ER-derived membranes
  3. L. monocytogenes - secretes LLO and PlcA & PlcB to escape the phagosome, in the cytoplasm they replicate and become motile by using actin ‘comet tails’ to generated by the effector ActA
27
Q

Tuberculosis is caused by what bacterium?

A

Mycobacterium tuberculosis

28
Q

Features of M. tuberculosis?

A
  • Gram positive
  • Non-motile
  • Pleomorphic rods
  • Acid fast is the staining method
  • Very slow growing (difficult to treat)
  • Very low infectious dose - highly infectious
29
Q

What group of people are particularly susceptible to developing TB?

A

HIV AIDS sufferers

30
Q

What makes TB difficult to treat?

A

Because it is very slow growing (generation time of about 20 hours)
Need a 6-12 month regiment of treatment

31
Q

What percentage of people infected by M. tuberculosis will develop TB?

A

10%

32
Q

True or False: There is an increase in multi-drug resistance strains of TB

A

True - very scary!

MDR (multi-drug resistant; resistant to the 2 most powerful (rifampicin/isoniazid) anti-TB drugs) and XDR (extensively-drug resistant; MDR with additional resistance to a further 2 of the core anti-TB drugs) strains.

33
Q

How does M. tuberculosis cause disease?

A

Cells infect macrophages, prevent maturation of phagosome, attract T cells which calcify the infected area, can get necrosis & lung damage. Lesions in lung associated with calcification of macrophages

34
Q

Treatment for TB?

A

Antibiotics i.e. Rifampicin & Isoniazid (6-month drug regimen)

35
Q

How many TB patients will die within weeks/months if disease isn’t treated (by antibiotics)?

A

1 in 3

36
Q

TB disease either goes into?

A

Remission (halts, asymptomatic but bacteria still present) or becomes chronic and more debilitating with cough, chest pain & bloody sputum

37
Q

How does L. pneumophila replicate in water reservoirs?

A

By infecting amoeba

38
Q

What is the T4SS’s roles

A

The T4SS secretes effector proteins into the phagosome, and these interact w the phagosomal membrane etc

Alter signalling pathways within the macrophage to change trafficking of the phagosome- so Legionella can live and replicate in it

39
Q

What is the most successful bacterial pathogen known to man?

A

Mycobacterium tuberculosis

40
Q

How is TB spread?

A

Spreads through the air and usually infects the lungs although other organs may be affected

41
Q

Symptoms of TB

A

Early symptoms of active TB can include weight-loss, fever, night-sweats, and loss of appetite, or they may be vague and go unnoticed by the affected
individual