Lecture 3- C.tetani Flashcards

(54 cards)

1
Q

What family does c.tetani belong to

A

Coostridiaceae

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2
Q

Clostridium genus obligate or facûltative anaerobic sporeformer

A

OBLIGATE ANAEROBIC

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3
Q

Clostridium genus gram+/-?

A

Gram positive

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4
Q

Size of Clostridium genus

A

1um x 20um (BIG)

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5
Q

Specific base frequent in Clostridium genus

A

Low G/c content

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6
Q

Where are Clostridium genus found

A

Ubiquitous

Gut, soil

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7
Q

What does Clostridium genus use as fińal electron acceptor in obtaining energy

A

Sulfate to get ATP

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8
Q

Clostridium genus are generally saprophytes but which are pathogenic

A

Botulinum, tetani, perf

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9
Q

What two routes do Clostridium genus obtain ATP

A

Fermentation or anaerobic respiration.

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10
Q

What occurs in anaerobic respiration for c genus

A

Electron accepter is exogenous and reduce sulfate to sulphite. Sulfate is less oxidising than oxygen so less ATP produced

Take 2-3 days to grow

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11
Q

What occurs in fermentation route for c genus

A

ELECTRON ACCEPTOR ENDOGENOUS (opposite to anaerobic respiration)

Don’t use electron transport chain.
Glucose get oxidised to first intermediate and oyrvate act as a final electron acceptor. Energy produce substrate level phosphorylation

Pyruvate further reduced to get more fermentation products

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12
Q

What are Other fermentation products produced via c genus

A

Lactate, ethanol, propionic acid, acetic acid etc

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13
Q

Clostridia utilise a fermentation pathway to obtain an acid from pyruvate. What is the pathway and the acid called

A

Butyric fermentation produce butyric acid from pyruvate

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14
Q

What unfavourable condition for c. Would form endospore

A

OXYGEN

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15
Q

What location of spores are present for c genus and name examples

A

C diff subterminal
Central spores
Tetani - terminal spores - chicken drumstick

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16
Q

What are the distinct components of the endospore for c genus

A

Exosporium - attach loosely to environment
Spore coat - huge chunk of protein
Cortex - huge layer of peptidoglycan
Core - DNA , ribosomes. LOW H2O, small acid soluble spore proteins (SASP) and DPA-Ca2+

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17
Q

Name function of two key components of spore core ; SASPS and DPA- ca2+

A

SAPS- saturates DNA so protection from wet/dry heat

DPA- ca2+ bind free H20 leading to dehydration so protection against wet heat

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18
Q

Describe the process of spore formation

A

1- dna condenses and in centre of cell (become mother cell)
2- dna divide in two.
3- mother cell invaginates and become forespore
4- mother cell membrane grow and engulf spore so two layers of membrane
5- layer of peptidoglycan form between two membranes to make cortex
6- DPA in core and then calcium move into cell and lead to water removal
7- protein coat may make it mature. May form exosporium.
8- lytic enzymes destroy mother cell and spore released

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19
Q

Clostridium sp. germination of spores process

A

1- exposure to specific GERMINANT and activation (irreversible)
2- partial rehydration. DPA- ca2+ release. Loss of some resistance
3- cortex hydrolysis. Full core rehydration and expansion
4- (outgrowth). SASP degradation, metabolism can divide via binary fission, escape from spore coat and divide

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20
Q

Once germinant has bound to receptor is this process of germination reversible

A

NO - irrevsible once started

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21
Q

Name historical derivation, spore structure, disease caused and frequency of disease for c. Botulinum

A

HD- sausage
SS - oval, subterminal
DC- Botulism (foodborne, infant, wound)
FOD- Uncommon

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22
Q

Name historical derivation, spore structure, disease caused and frequency of disease for c diff

A

HD - difficult - hard to grow
Ss- oval, subterminal
Dc- AAD (antibiotic associated diahorrea and PMC
FOD - very common

23
Q

Name historical derivation, spore structure, disease caused and frequency of disease for c perf

A

HD- breaking through
SS- large rectangular
DC- Gi infection
FOD - Common

24
Q

Name historical derivation, spore structure, disease caused and frequency of disease for c tetani

A

HD - tension
SS - round terminal (drumstick)
DC- tetanus
FOD - uncommon

25
Who studied a man with a dart wound which led to spastic paralysis in face and back
Hippocrates
26
Who discovered clostridium tetani in 1884 by injecting soil into mice to get paralysis?
Arthur Nicolaier
27
Who discovered that soldiers were getting ill on the waterloo battlefield in 1832 and drew the symptoms?
Sir charles bell
28
Who first isolated c tetani from a soil sample and described them as obligate anaerobes?
Shibasaburo kitasato
29
Displacement activity: when is a chair not a chair
Who knows. If you're smart enough to answer you're probably a genius
30
Where are the spores for c tetani?`
Round terminal spores drumstick
31
What virulence factors does c tetani have?
A)spore former which can contaminate wounds | B)exotoxins TETANOLYSIN and TETANOSPASMIN (which causes spasmic paralysis)
32
Name 7 counties where c tetani is highly prevalent?
India, china,Africa (ghana,egypt,zaire,mali)
33
How many cases are theee worldwide?
50 million
34
How many deaths are there worldwide and how many are in neonates?
Half a million deaths. 60 thousand in neonates
35
Where does 80 percent of the cases occur
Africa/south east asia
36
How many cases were there in the uk in 2014 and generally in USA?
UK: 3-5 CASES PER ANNUM USA:50-100 CASES PER ANNUM
37
Name some key risk factors for c tetani infection
Lack of immunisation Age over 60 years (Age 60-65 need to get a booster vaccination ideally) Open wounds contaminated with soil/manure Skin/tissues puncture eg. Rusty metals, thorns and ear piercings Childbirth especially in africa and india - rural african communities use cow dung and soil put on umbilical cords of youngsters to help heal but the spores get in and cause neonatal tetanus
38
Why does the location of c tetani spore germination suggest it is an anaerobic organism?
Germinates in deep areas of tissue
39
How does c tetani adhere to host cells?
Fibronectin binding proteins S-layer surface proteins (also help evade phagocytosis) Peritrichous flagella - movement and attach
40
What four things are used by c tetani to increase its damage?
Haemolysin III - pore forming Tetanolysin - pore forming Collagenase spread through deeper tissue Tetanospasmin yassss
41
Describe key characteristics of tetanospasmin
It is a type lll toxin. Has alpha beta sub units (KDa).
42
What the lethal dose of this neurotoxin tetanospasmin?
2.5 nanograms per kilogram. Eg. 175ng will kill a 70 kg human. OMG RIGHT. Second most potent toxin
43
Describe the mechanism of action of tetanospasmin
Prevents inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine from being releases( spastic paralysis). Organism release tetanospasmin in stationary phase, transport to CNS, peripheral NS via vasculature
44
Describe the molecular weight and function of both the light and heavy chain of tetanospasmin
Heavy chain - carboxyl and amino group 100kda combined carry toxin to neurones. Carboxyl bind to the cell and amino group help the toxin get into the cell across membrane Light chain - active part. Has activity in neurones. Destroy component synaptobrevin (proteolytic activity). Contain one zinc atom
45
What happens to disulphides bridges inside neurones
Link heavy and light chain together. Inside neurone get refuge which frees light chain
46
Describe normal MOA for muscle contractions before tetanospasmin
Neuron; vesicles dock via snare protein complexes (v-snare/T -share) and release Ach - muscle contract Inhibitory interneuron - vesicles containing GABA/glycine dock via snare complex and release inhibitory neurotransmitters by exocytosis
47
What is the vsnare
Synaptobrevin
48
Describe tetanospasmin MOA
A subunit (light chain) cleaves synaptobrevin (v snare) and prevents DOCKING of INHIBITORY neurotransmitters vesicle to presynaptic membrane V snare form snare complex with T snare on pre synaptic terminal Permentant contraction
49
What are two main symptoms of generalised tetanus (80% of cases) and what are other types (20%)
Lockjaw - trismus Spascity in head and spinal column (opisthotonus) 20% - cephalic tetanus, localised tetanus, neonatal
50
What is first symptom of general tetanus
Lockjaw or trismus. Incubation period 8-12 days post puncture Cannot eat, to swallow or speak Result in risus sardonicus - sardonic smile
51
Describe sardonic smile
Abnormal sustained spasm of facial muscle - appear lie grinning - raised eyebrows and open 'grin' - appear scary
52
How is tetanus diagnoses
CLINICAL PRESENTATION and combo of below - PATIENT HISTORY - recent injury - 70% cases identify injury. Or incomplete tetanus immunization - specific symptoms progressive muscle spasms ( starting in facial region, especially lockjaw and progressing outward from the face to include all muscles of the body - non specific - fever, high BP, irregular heartbeat
53
What is the 3 fold treatment objectives
1- limit growth via antibiotics - penicillin, metranidizol, gentomyocin to kill it 2- neutralise circulating toxin. : TIG - tetanus immunoglobulin 3- supportive measures - wound cleaning, valium, ventilator support
54
How is tetanus prevented
VACCINE -toxoid (formaldehyde inactivated) given as part of childhood immunisation programme (DTaP); diphtheria, tetanus, pertussis (whooping cough) in 5 doses. Primary course - given in arm or thigh to children aged 2,3,4 months Fourth dose - 3 years and 4 months Fifth dose - 13- 18 years Booster - international travel e.g africa, asia to areas