Lecture 31 - Chlamydia Flashcards

1
Q
Chalmydia
1)
2)
3)
4)
A

1) A large group of obligate intracellular pathogens
2) Lack multiple metabolic and biosynthetic pathways
3) Depend on host for ATP, amino acids
4) Genome encodes many nutrient transporters

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2
Q

Size of chlamydia genome

A

1-1.3 MB

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3
Q

Chlamydia species that normally infect humans
1)
2)

A

1) C. trachomatis

2) C. pneumoniae

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4
Q

Chlamydia species that infect immunosuppressed humans
1)
2)
3)

A

1) C. psittaci
2) C. abortus
3) C. felis

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5
Q

Type of evolution that chlamydia has undergone

A

Reductive evolution

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6
Q

Number of different C. trachomatis serovars

A

19

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7
Q

Disease caused by C. trachomatis serovars A-C

A

Trachoma (a form of blindness)

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8
Q

Trachoma
1)
2)

A

1) Caused by C. trachomatis serovars A-C

2) Currently 1.3 million people blind, 40 million with active disease

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9
Q
Causes of blindness form trachomatis
1) 
2) 
3) 
4)
A

1) Recurrent inflammation leads to conjunctival scarring
2) Entropion
3) Trichiasis (scratches the cornea, leads to ulceration)
4) Leads to corneal opacity

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10
Q

Entropion

A

When eyelids turn inwards to eye

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11
Q

Trichiasis

A

When eyelashes scratch eye

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12
Q
How might blinding trachoma be transmitted?
1) 
2) 
3) 
4)
5)
A

1) eye-eye contact during sleep, play
2) Spread of infected ocular or nasal secretions on fingers
3) Indirect spread on fomites (EG: face cloth)
4) Eye-seeking flies (passive vector)
5) Nasopharyngeal infections by aerosol

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13
Q

WHO SAFE strategy for trachomatis

A

Surgery for trichiasis
Antibiotic therapy
Facial cleanliness
Environmental improvements

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14
Q
Environmental improvements to decrease blinding trachoma 
1) 
2) 
3) 
4)
5)
A

1) Promote better personal and environmental hygiene
2) Improve water quality, supply
3) Improved access to latrines
4) Reduce fly population
5) Reduce crowding

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15
Q

Diseases caused by C trachomatis serovars D-K

A

Urogenital tract infections

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16
Q

C trachomatis serovars that cause urogenital tract infections

A

Serovars D-K

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17
Q

Leading cause of bacterially-caused STIs worldwide

A

C trachomatis serovars D-K

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18
Q

Estimated number of people infected with C trachomatis A-K each year

A

105 million

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19
Q

Number of C trachomatis D-K infectinos that are asymptomatic

A

Men - 50%

Women - 70%

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20
Q

C trachomatis D-K symptoms in men

A

Urethritis (can lead to discharge)

Proctitis

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21
Q
C trachomatis D-K symptoms in women
1) 
2) 
3) 
4)
A

1) Cervicitis (can lead to ascending infection, commonly endometritis)
2) Pelvic inflammatory disease (caused by ascending infection)
3) PID can lead to fallopian tube scarring and infertility
4) Proctitis

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22
Q

Disease caused by C trachomatis serovars L1-L3

A

Lymphogranuloma venereum

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23
Q
Lymphogranuloma venereum
1) 
2) 
3) 
4)
5)
A

1) Caused by C trachomatis serovars L1-L3
2) Invasive infection causing severe inflammation
3) Causes systemic infection, genital ulcers
4) If untreated, leads to chronic granulomatous inflammation, lymphatic obstructions, fibrosis, formation of strictures
5) Ano-rectal disease leads to acute haemorrhagic inflammation

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24
Q

Difference between C trachomatis serovars L1-L3 and other serovars

A

All other serovars only infect epithelial surfaces

Serovars L1-L3 can invade beyond epithelial surfaces

25
Q

Proportion of community-acquired pneumonia caused by C pneumoniae

A

10%

26
Q

How is C pneumoniae spread?

A

Aerosolised secretions

27
Q

What is possibly associated with C pneumoniae infection?
1)
2)
3)

A

Chronic human diseases:

1) Cardiovascular disease
2) Arthritis
3) Diabetes

28
Q

What is persistence?

A

A non-replicating state of C pneumoniae, triggered by lack of nutrients in a cell (particularly lack of tryptophan)

29
Q
C pneumoniae persistence mechanism
1) 
2) 
3) 
4)
5)
A

1) Infected cell releases IL-1, IL-6, triggers IFNg release
2) IFNg causes intracellular increase in IDO
3) IDO leads to decrease in cytosolic tryptophan, which C pneumoniae needs to survive
4) C pneumoniae enters persistence state (large, non-replicating cells)
5) Host thinks that infection has been cleared, IFNg decreases, tryptophan returns

30
Q

Chlamydia species infecting koalas
1)
2)

A

1) C percorum (keratoconjunctivitis, infertility in females)

2) C pneumoniae (rhinitis, pneumonia)

31
Q

Forms of Chlamydia
1)
2)

A

1) Elementary bodies

2) Reticulate bodies

32
Q
Elementary bodies 
1) 
2) 
3) 
4)
A

1) Spherical, 0.2-0.3 micrometers
2) Electron-dense (eccentric core of condensed DNA, chromatin)
3) Osmotically stable, less permeable than reticulate bodies (persists in environment)
4) 1:1 RNA:DNA (metabolically inert)

33
Q
Reticulate bodies 
1) 
2) 
3) 
4)
A

1) Spherical, 0.5 - 1.6 micrometers
2) Less electron-dense cytoplasm
3) Not infectious
4) Replicating stage within host cell

34
Q

What surrounds the inclusion?

A

Golgi fragments

35
Q

Inclusion

A

Name of the vacuole in which Chlamydia lives in a host cell

36
Q

Coxiella small-cell variant equivalent in Chlamydia

A

Elementary bodies

37
Q

What stimulates the formation of elementary bodies from reticulate bodies?
1)
2)

A

1) Drop in nutrients in host cell

2) When there are enough bacteria in an inclusion that they begin falling off the vacuole membrane

38
Q

What happens when there are a certain number of elementary bodies in an inclusion?

A

Host cell is lysed, elementary bodies infect new cells

39
Q

Can chlamydia infect many cells?

A

Yes. Can infect most cells in the lab

40
Q
Chlamydia cell entry
1) 
2) 
3) 
4)
A

1) Heparan sulphate proteoglycan interaction, followed by high-affinity interaction with a secondary receptor
2) Second receptor can be: mannose receptor, oestrogen receptor, platelet-derived growth factor receptor
3) Bacterial adhesins (major outer membrane protein, OmcB, PmpD)
4) Entry into non-phagocytic cells mediated by small GTPase-dependent reorganisation of the cytoskeleton

41
Q

Chlamydia establishment of an intracellular niche
1)
2)
3)

A

1) Inclusion avoids fusion with lysosomes (active modification of host trafficking, innate properties of elementary body)
2) Inclusion trafficks along microtubules to a peri-Golgi location (progressive fragmentation of Golgi)
3) Directs homotypic fusion of inclusions

42
Q

Homotypic fusion of inclusions

A

Inclusions fuse together to form one large inclusion

43
Q

Which type of secretion system does Chlamydia use?

A

T3SS

44
Q

What makes the T3SS of Chlamydia unique?

A

Genes are clustered in at least 4 different parts of the genome

45
Q
Chlamydia T3SS functions
1) 
2) 
3) 
4)
A

1) Just after entering host - Preloaded T3SS promote survival, EB to RB change
2) Early RBs seek to maximise contact between T3SS and inclusion membrane
3) Early inclusion - Neosynthesised T3SS promote exponential RB division
4) Late inclusion - Number of bacteria cause detachment from inclusion membrane. This leads to expression of late-stage effectors from T3SS, RB change to EB

46
Q

Number of effectors encoded by T3SS

A

50-100

47
Q

Invasion effector protein

A

TARP - Translocated actin-recruiting phosphoprotein

48
Q
Translocated actin-recruiting phosphoprotein 
1) 
2) 
3) 
4)
A

1) Invasion effector in Chlamydia
2) Secreted within minutes of entry to host cell
3) Recruits actin, is capable of nucleating filaments
4) Importance is demonstrated with neutralising antibodies

49
Q
Effects of Chlamydia effector proteins
1)
2)
3)
4)
A

1) Invasion
2) Prevent fusion of inclusion and lysosome
3) Divert host trafficking to provide nutrients and constituent molecules to inclusion
4) Localisation of inclusion membrane

50
Q
Inc proteins 
1) 
2) 
3) 
4)
A

1) Inclusion proteins
2) Cohort of effectors that localise the inclusion membrane
3) Characterised by inclusion localisation and bilobed hydrophobic domain of ~60 residues
4) Target Rab GTPases, SNARES, cytoskeletal proteins

51
Q
IncA
1) 
2) 
3) 
4)
A

1) Role in homotypic fusion of inclusions
2) Has SNARE-like motifs
3) Inhibits fusion of membranes that use endocytic SNARES
4) Role in homotypic fusion shown using microinjection of neutralising antibodies

52
Q
IncD
1) 
2) 
3) 
4)
A

1) Binds to CERT from host cell
2) CERT transports ceramide between ER and Golgi
3) Allows Chlamydia to acquire ceramide, and synthesise cholesterol from it
4) IncD binds CERT because ER-inclusion contact sites are formed upon C. trachomatis infection

53
Q

Difference between Coxiella and Chlamydia secretion systems

A

Coxiella uses a T4SS, Dot/ICM, which is only activated sometimes

Chlamydia uses a T3SS, is active all the time

54
Q

Why are Chlamydia capable of recombination?

A

Genome possesses DNA repair proteins

55
Q

Transformation system for placing plasmids in Chlamydia

A

Calcium chloride treatment and E coli-C trachomatis shuttle plasmid

56
Q

Agent used for chemical mutagenesis of Chlamydia

A

Ethyl methanesulphonate (a chelating agent)

57
Q

How is ethyl methanesulphonate used?

A

Induces mutations in Chlamydia genome

Culture mutants, look for abnormal inclusions

58
Q

Proof of principle of Chlamydia mutation

A

Isolation of a tryptophan-synthase null mutant, that was susceptible to IFNg-induced tryptophan starvation

59
Q

How can chalmydia be watched in real time?

A

Fluorescent stains