Hayley Schmaley Flashcards

1
Q

Q fever

A

50% seroconvert asymptomatic
50% experience Acute Q fever - influenza like
2% have chronic Q fever: endocarditis, difficult to treat (long term antibiotic treatment)
15% have long-term complications e.g. chronic fatigue

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2
Q

Q fever transmission

A

Extremely infectious - 1 bacterium can cause disease
ticks are a reservoir but do not vector disease to humans
Farm animals –> excretion –> transmission (aerosols mostly/ingestion) –> humans (farmers, vets, abattoir workers)
Coxiella environmentall resistant
Q-vax: formalin-inactivated whole cell C.burnetii

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3
Q

Coxiella biological weapon

A

Very infectious
Environmentally resistant
Easily spread
Incapacitating agent - significant public health outbreak
Developed by uSA and soviet union during cold war & Japan

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4
Q

Netherlands coxiella outbreak

A

Densely packed farm animals + houses
Farmers noticed higher numbers of spontaneous abortions
Animals underwent mass vaccinations
Peak during dry hot weather

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5
Q

Coxiella replication

A

Intravacuolar

Phagosome –> early endosome –> late endosome –> lysosome (4.5pH, proteolytic enzymes, most bacteria die)

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6
Q

SCV

A

Small cell variant
Version that is environmentally resistant - heat, UV light, dessication, osmotic shock
–>LCV

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7
Q

LCV

A

large cell variant
Bigger bacterium
Metabolically active

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8
Q

Coxiella: replication in phagolysosome

A

Basic proteome
Production of acid phosphatase - inhibit NADPH oxidase limiting ROS production
DNA repair system upregulated under oxidative stress
Metabolically active at low pH

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9
Q

Dot/Icm coxiella

A

Similar to legionella - functionally analogous, effector proteins are very different
Spans multiple membranes
Can’t replicate without Dot/Icm
Won’t start translocating effector molecules until its in lysosome

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10
Q

Axenic growth coxiella

A

a lot of cysteine
5% cO2, low O2, 37C
ph~4.75

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11
Q

B-lactomase reporter assay

A

Introduce plasmid that encodes b-lactamase
CCF2-Am enters cell + light –> fluorescence (green)
B-lactamase cleaves B-lactam ring –> blue light

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12
Q

Dot/Icm effectors

A
Prevent host apoptosis
Contribute to fusogenicity of vacuole 
Mediate interaction with autophagosomes
Mediate cholesterol acquisition
130 effectors
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13
Q

Dot/Icm effector identification

A

genomic fragments digested –> cloned into reporter

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14
Q

Understanding coxiella effector functions

A

Examine localization e.g. mitochondria
Produce neutralizing antibodies
Biochemical and protein function studies

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15
Q

Rickettsiae general

A

Diverse collection of obligate intracellular GN
Include Rickettsiae, Ehrlichia and Oreintia genera
Zoonotic: exist in animals in the wild
Transmitted to humans via arthorpod e.g. ticks, lice, fleas

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16
Q

Rickettsiae biogroups

A
  1. Spotted fever e.g. Rocky mountain
  2. Typhus e.g. epidemic typhus
  3. scrub typhus
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17
Q

Rocky Mountain spotted fever

A

25% mortality rate, 4% with treatment

Rash: 2-5 days, centripetal spread

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18
Q

RMSF transmission

A

Tick bites
Summer association
Transovarial: parent to offspring arthropod
Trans-stadial: passage from one developmental stage to subsequent stage - larvae, nymph, adult (infects rodent)

19
Q

Epidemic typhus

A

Rickettsia prowazekii
Unsanitary conditions
Spread by lice - defecation, scratch, bacteria enter

20
Q

Brill-Zinsser disease (chronic epidemic typhus)

A

Fever, chills, headache, myalgia
Rash: centrifugal spread - trunk spread to extremities
Complications: myocarditis

21
Q

Rickettsia endothelial cell entry

A

SFG Rickettsia OmpB binds Ku70 on endothelium - component of DNA-dependent protein kinase
Cholesterol dependent
Breaks out of phagosome - phospholipase and haemolysin
Typhus: replicate in cytosol until host cell ruptures
SFG: mediate actin-dependent movement

22
Q

RickA

A

No Arp 2/3 in tails

Participates in invasion, not movement

23
Q

ScaA

A

Identified by bioinformatics

Nucleate unbranched actin filaments

24
Q

Rickettsia virulence factors

A

Type 4aSS: different to DotIcm, upregulated during intracellular growth in some species
Protein and DNA transfer

25
Q

Chlamydia

A

Obligate intracellular pathogen
Require host to replicate - vacuolar pathogen
Small genome - reductive evolution
Lack metabolic and biosynthetic pathways
Dependent on host - ATP, aa
9 species - 2 affect humans

26
Q

Chlamydia trachomatis

A

19 serovars based on outer membrane protein

27
Q

C.trachomatis A-C

A

Blinding trachoma:
leading cause of blidness
Severe problem in Aboriginal communities
Inflammation in the eye –>entropian (eyelid turns in), trichiasis (eyelashes touch eyeball) –> cornea undergoes trauma -> blindness
TRANSMISSION: close contact, fomites, flies, aerosol, secretions

28
Q

SAFE strategy

A

S: surgery
A: antibiotic distribution
F: facial cleanliness - remove source and transmission
E: environmental improvements - hygiene, decreasing flies, health education

29
Q

C.trachomatis D-K

A

Sexually transmitted form
Urogenital tract infection
70% women, 50% men infected are asymptomatic

30
Q

Chlamydia D-K Symptoms

A

Men: urethritis, proctitis
Women: Cervicitis, Pelvic inflammatory disease –> infertility, proctitis

31
Q

L1-L3 chlamydia

A

LGV:
Invasive –> severe inflammation
Systemic symptoms, genital ulcers
Can lead to chronic granulomatous inflammation, lymphatic obstructions, fibrosis and strictures

32
Q

Chlamydia pneumonia

A

Animal kingdom but species specific strains
Respiratory disease: 10% of community acquired pneumonia, asymptomatic
Transmission: aerosol
Link to chronic diseases: CVD, arthritis, diabetes

33
Q

C.pneumoniae persistence

A

Immune cell recruitment to site of infection
IFNg detected by infected cell –> upregulates IDO
IDO degrades tryptophan –> KYN –> less tryptophan
Bacteria detects low tryptophan (needed to replicate)
IFN decreases, IDO decreases, tryp increases –> reactivation of inection
Nonreplicating - not going to be affected by antibiotics

34
Q

Chlamydia - Koala

A

C.percorum: main agent, causes blindness and infertility in females
C. pneumoniae: rhinitis and pneumonia
Treatment: antibiotics intolerant, need to capture it (wild koalas stressed in captivity)

35
Q

Chlamydia developmental cycle

A

EB (elementary): infectious, environmentally resistant, smaller than RB
RB (reticulate body): replicative form

EB taken up by host cell –> start to revert to RB –> replicate –> revert back to EB when nutrients are taken up

36
Q

Elementary bodies

A

Not producing RNA, proteins
Metabolically inactive
Osmotically stable

37
Q

Reticulate bodies

A

Not infectious

More transcriptionally active

38
Q

Chlamydiae entry

A

Invade most cells
Initial interaction between heparan sulfate proteoglycans –> 2nd interaction (high affinity) - mannose, estrogen, platelet-derived growth factor receptor

39
Q

Chlamydiae intracellular niche

A
Avoids fusion with lysosome
Delayed maturation (EB?)
Actively modify host trafficking
Traffics along microtubules --> Golgi
Directs homotypic fusion of inclusion - multiple chlamydia will end up in same inclusion e.g. quorum sensing
40
Q

Chlamydiae T3sS

A

25 genes
Molecular syringe
Not encoded in pathogenicity island - spread throughout chromosome (4 gene clusters)
1.EB preloaded with T3S effectors
2. Maximum contact between early RB and inclusion membrane surfaces
3. RB replication - early inclusion
4. Physical detachment provokes T3S inactivation with induction of late effectors - mid to late inclusion

41
Q

T3SS effectors chlamydia

A

~50-100 effector proteins
Preloaded effectors/invasion: e.g. TARP:
Translocated actin-recruiting phosphoprotein - movement of vacuole

Prevent fusion between inclusion and lysosomes
Divert host cell trafficking to inclusion to provide nutrients and constituent molecules required for bacterial replication e.g. Inc Proteins - localize inclusion, Rab, SNARES

42
Q

IncA

A

Fusion of inclusions

Has SNARE like motifs

43
Q

IncD

A

Interact with ER and creating contact site where ER and inclusion are close
Interacts with CERT: transports ceramide between ER and Golgi (lipid building block)
CERT localises to inclusion and binds to IncD - Chlamydia can acquire ceramide