13. Legionella & TB Flashcards
What bacterium causes Legionnaire’s disease?
Legionella pneumophila
How does Legionella pneumophila cause Legionnaire’s disease?
Evasion of destruction by phagosome
Legionella only grow?
Intracellularly in macrophages - do not grow on agar plates
A non-pneumonic variant caused by the same species as Legionella pneumophila is called?
Pontiac fever
Non-pneumonic - found other places besides the lungs
Features of Legionella species?
- Poorly staining
- Obligate (needs cells to replicate in)
- Aerobic
- Gram negative bacilli
- Tricky to culture, visualise & stain
- Rod-shaped
Is L. pneumophila spore-forming?
No
Symptoms of Legionnaire’s disease?
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)
Has person-person spread of Legionnaire’s disease ever been demonstrated?
No
Death rate of those identified with Legionnaire’s?
20%
10,000 - 100,000 cases in US
How is Legionnaire’s contracted?
By inhaling airborne water droplets containing Legionellae
Legionnaire’s disease is particularly associated with?
Man made things e.g cooling water used in air conditioning
Where does infection by Legionella begin in the body?
Lower respiratory tract
Legionnaire’s disease pathogenesis:
- 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
Why is infection by Legionella difficult to diagnose?
Because they only grow inside macrophages
What happens if phagocytosis is prevented by treatment with cytochalasin?
The bacteria (Legionella) are denied access to the intracellular environment and growth does not occur
True or False: Legionella do not replicate in water but can infect amoeba and multiply
True
Amoeba are a training ground for intracellular bacteria.
What are the most important virulence factors in Legionella?
Those that help modify the phagosome
What does Legionella use to secrete proteins into the phagosome itself?
Type 4 Secretion System
What is the most important virulence factor in Legionella pnuemophila?
Dot/Icm T4SS
Dot = defect in organelle trafficking, Icm = intracellular multiplication
What gene has been shown to have some role in adhesion, invasion and phagosome trafficking in macrophages and amoeba?
RtxA gene
What has pore-forming activity and is required for bacterial egress from mammalian or protozoan cells after bacterial replication is complete?
IcmT
Different strains of Legionella have different…
effector profiles
The symptoms of Legionella infection undoubtedly result from a combination of what?
- Physical interference with oxygenation of blood
- Ventilation-perfusion imbalance in the remaining lung tissue, and
- Release of toxic products from bacteria & inflammatory cells
What greatly reduces the death rate of Legionnaire’s?
Prompt treatment with erythromycin
Are there vaccines available for Legionnaire’s disease?
No
What 3 bacteria undergo phagosome modification (central part of virulence strategy)?
- S. typhimurium - T3SS effector proteins secreted to block phagosome maturation resulting in the formation of SCV (salmonella containing vacuole) formation
- L. pneumoophila - T4SS effector proteins secreted to prevent fusion of LCV (legionella containing vacuole) with endolysosomal compartments, and promotes fusion with ER-derived membranes
- 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
Tuberculosis is caused by what bacterium?
Mycobacterium tuberculosis
Features of M. tuberculosis?
- Gram positive
- Non-motile
- Pleomorphic rods
- Acid fast is the staining method
- Very slow growing (difficult to treat)
- Very low infectious dose - highly infectious
What group of people are particularly susceptible to developing TB?
HIV AIDS sufferers
What makes TB difficult to treat?
Because it is very slow growing (generation time of about 20 hours)
Need a 6-12 month regiment of treatment
What percentage of people infected by M. tuberculosis will develop TB?
10%
True or False: There is an increase in multi-drug resistance strains of TB
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.
How does M. tuberculosis cause disease?
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
Treatment for TB?
Antibiotics i.e. Rifampicin & Isoniazid (6-month drug regimen)
How many TB patients will die within weeks/months if disease isn’t treated (by antibiotics)?
1 in 3
TB disease either goes into?
Remission (halts, asymptomatic but bacteria still present) or becomes chronic and more debilitating with cough, chest pain & bloody sputum
How does L. pneumophila replicate in water reservoirs?
By infecting amoeba
What is the T4SS’s roles
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
What is the most successful bacterial pathogen known to man?
Mycobacterium tuberculosis
How is TB spread?
Spreads through the air and usually infects the lungs although other organs may be affected
Symptoms of TB
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
