Hayley Schmaley Flashcards
Q fever
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
Q fever transmission
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
Coxiella biological weapon
Very infectious
Environmentally resistant
Easily spread
Incapacitating agent - significant public health outbreak
Developed by uSA and soviet union during cold war & Japan
Netherlands coxiella outbreak
Densely packed farm animals + houses
Farmers noticed higher numbers of spontaneous abortions
Animals underwent mass vaccinations
Peak during dry hot weather
Coxiella replication
Intravacuolar
Phagosome –> early endosome –> late endosome –> lysosome (4.5pH, proteolytic enzymes, most bacteria die)
SCV
Small cell variant
Version that is environmentally resistant - heat, UV light, dessication, osmotic shock
–>LCV
LCV
large cell variant
Bigger bacterium
Metabolically active
Coxiella: replication in phagolysosome
Basic proteome
Production of acid phosphatase - inhibit NADPH oxidase limiting ROS production
DNA repair system upregulated under oxidative stress
Metabolically active at low pH
Dot/Icm coxiella
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
Axenic growth coxiella
a lot of cysteine
5% cO2, low O2, 37C
ph~4.75
B-lactomase reporter assay
Introduce plasmid that encodes b-lactamase
CCF2-Am enters cell + light –> fluorescence (green)
B-lactamase cleaves B-lactam ring –> blue light
Dot/Icm effectors
Prevent host apoptosis Contribute to fusogenicity of vacuole Mediate interaction with autophagosomes Mediate cholesterol acquisition 130 effectors
Dot/Icm effector identification
genomic fragments digested –> cloned into reporter
Understanding coxiella effector functions
Examine localization e.g. mitochondria
Produce neutralizing antibodies
Biochemical and protein function studies
Rickettsiae general
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
Rickettsiae biogroups
- Spotted fever e.g. Rocky mountain
- Typhus e.g. epidemic typhus
- scrub typhus
Rocky Mountain spotted fever
25% mortality rate, 4% with treatment
Rash: 2-5 days, centripetal spread