Lecture 30 - Legionella Flashcards Preview

MIIM20002 - Microbes, Infections, Responses > Lecture 30 - Legionella > Flashcards

Flashcards in Lecture 30 - Legionella Deck (48):
1

Where does the causative agent of Legionaire's disease come from?

Environment
• soil
• water

No human or animal reservoir

2

Describe Legionnaire's disease

Acute form of pneumonia
- requires serious medical intervention

3

What is Pontiac fever?

Milder form of Legionnaire's disease
• flu like
• self limiting

4

What determines whether the infection causes Legionnaire's or Pontiac fever?

Unclear
• patient factors?
• strain?

5

How many species of Legionella are there?

more than 50

6

Which is the most common species of Legionella?

Legionella pneumophila

7

Which serogroup is the most common cause of Legionnaire's disease?

Serogroup 1

90 % of cases

8

Why is it an emerging pathogen

Only been identified from the late 1970's

Only recently has it caused outbreaks, due to man-made water systems

9

Describe the Gram classification of Legionella

Gram negative

10

Describe the trends of Legionnaire's disease in AUstralia

Not very common
• only a few cases reported
• since most people clear the infection

2000
• very large outbreak at Melbourne Aquarium

11

Describe the result of most cases of infection with Legionella

Most people will feel ill, but then clear the infection

Tip of the iceberg:
• immunocompromised will get full blown disease

12

Describe what happened at the Melbourne Aquarium

2000
Just before the Aquarium opened
Legionella in the air conditioning
SPread to many people working around the site

Since then, tight regulations on cooling towers etc.

13

What are the different places where Legionella can be picked up?

Community acquired
• eg Melbourne Aquarium

Nosocomial

14

How is Legionella transmitted?

Aerosols
Man made water sources
• cooling towers
• spas
• fountains
• car wash
• showers

Cannot be transferred from person to person

15

What are the risk factors for Legionnaire's disease?

• Immune deficiency
• Drinking
• Male gender
• Old age
• Co-morbidity:
- smoking
- poor lung function

16

Why is Legionella called an accidental pathogen?

Infection in a human is a dead end for the pathogen

It can not be spread further from there

17

Why does Legionella grow in man made water sources?

Higher than normal temperature
Favourable conditions for the bacteria

18

What are some important Legionella outbreaks?

Philadelphia 1976
• American Legion convention

Netherlands, 1999
• Whirlpool spa

19

How are water sources tested?

Water sample taken
Growth on medium
Viable count test

20

How did they identify Legionella initially?

Philadelphia outbreak
Initially, didn't know what is was
Took a biopsy
Growth in pig cells

21

How is Legionella pneumophila cultured?

Charcoal agar (iron and cysteine)
• because it is very fastidious

Dessicated white colonies

22

How is Legionella treated?

Antibiotics - Erythromycin
Macrolides
Auinolones

23

How is Legionella detected in the lab?
Describe the features of this test

Urine antigen test
• very high specificity
• rapid
• non-invasive
• only serogroup 1

24

What is seen in the urine in people with Legionella infection?

LPS in the urine

25

What does high specificity of a test mean?

Very few false positives

26

Describe the pathogenesis of Legionella

1. Taken into lung
2. Taken up by alveolar macrophages
3. Avoids phagolysosome fusion
4. Recruits host cell vesicles
5. Recruits rough ER into the vaculole
6. Grows and replicates in alveolar macrophages
7. Macrophage dies
8. Released to infect more macrophages

27

Describe the appearance of the alveolar macrophage after infection with Legionella

Very large vacuole forms
Full of Legionella bacteria

28

How does Legionella survive in the environment?

Not free living
Must infect amoebae
• survives and resplicates in amoebae
• kills amoebae and spreads further

29

What are amoebae?

Single celled phagocytes

Take up bacteria as a food source

Training ground for pathogens

30

Describe the role of amoebae in transmission of Legionella

• Amoebae in cooling towers
• Amoebae protect the bacteria from disinfectants and biocides

31

What is the difference between Legionella and other intracellular bacteria pathogens?

Legionella not at all evolved to survive in human cells

32

Describe normal phagocytosis

1. Phagosome formed around bacteria
2. Fusion of lysosomes
3. Early endosome → lysosome
4. Degradation of bacteria
• hydrolytic enzymes
• ROS
• RNS

33

How does Legionella avoid killing once phagocytosed?

• prevents lysosomal fusion
• recruitment of ER exit vesicles
• vesicles coat the outside of the vacuole
• vacuole look like ER → obtains ribosomes, allowing replication

34

What are LCVs?

Legionella containing vacuoles

• don't acidify
• don't fuse with lysosomes
• come to resemble rER

35

What makes the LCV resemble ER?

Retains ER markers on the membrane

1. Type IV secretion system in membranes of bacterium
2. Interacts with host cell membrane
3. Transfers proteins into the host cell

36

What is the name of the T IV SS of Legionella?

Dot / Icm secretion system
Defective organelle trafficking
Intracellular multiplication

37

Where is Dot/Icm SS found?

Poles of bacterium

38

How many different proteins are injected by the type IV SS?

300 'effector' proteins

39

What do the effector proteins do?

• similar to eukaryotic proteins
• mimic eukaryotic function

→ take over eukaryotic cell processes such as:
• mitochondrial activity
• gene transcription and translation
• apoptosis
• GTPase activity
• vesicle trafficking

40

Do many bacteria have these 'eukaryotic proteins'

No, almost exclusively Legionella have them

Due to close evolution of Legionella with amoebae

41

Describe how Legionella targets host GTPases

Legionella has taken up a Sec7 domain from a eukaryotic cell

Sec7 domain in the RalF
RalF is a Guanine exchange factor

1. RalF recruits Arf1 (a GTPase) to the LCV
2. RalF activates Arf1
3. Arf1 controls vesicle fusion

42

What is the function of GTPases?

Regulate many processes in cells
• vesicle trafficking, for example

1. GEF swaps GDP → GTP
2. GTPase now active

43

What is Arf 1?

A GTPase in the host cell
• controls vesicle fusion

44

What is a GEF?

Guanine exchange factor

Activates GTPase

45

What is Sec7?

A domain in RalF (a GEF in Legionella)

46

Describe the immune response to Legionella

• inflammatory cytokine response
• neutrophils
• NK
• T and B cells response

47

Which cytokines are required for an effective immune response?

TNF, IL-12, IFN-gamma

48

What is required for clearance of Legionella?

T and B cell responses