Clostridium and Corynebacterium

path micro exam 2

what is the general gram staining for clostridium?

gram positive RODS

can clostridium species form spores?

yes!

what is the metabolic behavior for clostridium?

anaerobic

what is the most common form of disease for C. botulinum?

food-borne botulism

what kind of toxin is C. botulinum toxin?

A-B toxin

what are the subunits of the A-B toxin and what do they do? (in c. botulinum)

subunit A: (acting) zinc-endopeptidase activity

subunit B: (binding) binds to sialic acid receptors/glycoproteins on the surface of motor neurons; nontoxic and protects A subunit;

where does the A-B toxin reside/remain? (in c. botulinum)

neuromuscular junction

what is the mechanism behind the botulinum toxin? (~3 steps)

1. endopeptidases inactivates proteins that regulate release of acetylcholine

2. neurotransmission at peripheral cholinergic synapses block = blocks acetylcholine release

3. flaccid paralysis (no muscle contraction = relaxation)

what are the 4 forms of botulism?

• classic/foodborne

• infant

• wound

• inhalation

what is indicative of progressive botulism?

bilateral descending weakness of peripheral muscles

the neurotoxin is reversibly or irreversibly bound to neurons

irreversibly; for recovery neurons have to be regenerated

what is infant botulism also known as?

floppy baby syndrome

how do infants obtain botulism?

HONEY, spores or in milk powder

there are 7 antigenically versions of botulinum toxin, which are found in humans?

A B E F

what can be used to inactivate the unbound A-B toxin, and which versions are they effective against?

trivalent botulinum antitoxin; A B E

what clostridium species is part of the normal intestinal flora of some?

C. difficile

where/how does disease from C. difficile occur?

proliferation in the COLON

what are the 2 toxins that c. difficile produces?

toxin A and toxin B

what is toxin A? and what does it do?(in c. difficile)

enterotoxin

• chemotactic for neutrophils (stimulates the infiltration of them into ileum),

• produces a cytopathic effect (disrupts tight junctions, and increases GI wall permeability —> diarrhea)

what is toxin B? and what does it do? (in c. difficile)

cytotoxin

• depolymerizes actin (destruction of cellular cytoskeleton)

what is the most severe form of C. difficile disease?

pseudomembranous colitis

where can pseudomembranous colitis be observed and does it look?

colonoscopy

white plaques over intact colonic tissue — fibrosis

what species of clostridium rarely forms spores?

clostridium perfringens

which type of C. perfringens is common in intestinal tracts of humans and animals?

Type A

what are the toxins of C. perfringens? (5)

alpha

beta

epsilon

iota

enterotoxin

what is the most common disease of c. perfringens?

myonecrosis

what is myonecrosis characterized by?

intense pain, muscle necrosis, shock, renal failure

which toxin is seen in type E (c. perfringens), what does it do?

iota, necrotic activity and increases vascular activity

which toxin is primarily produce by Type A (c. perfringens)? and what does it do?

enterotoxin, binds to receptors on small intestine (brush border membrane) and acts a super antigen

• activity is increased when exposed to trypsin

• produced when vegetative state —>spore

what is the epsilon toxin and what does it do?

a protoxin that is activated by trypsin, increases the vascular permeability of GI wall

what is the alpha toxin and what does it do?

phospholipase C or lecinthinase

• mediates hemolysis

• increased vascular permeability/bleeding

• tissue destruction

• hepatic toxity

• myocardial dysfunction

what does the beta toxin do?

intestinal stasis, loss of mucosa, progresses necrotizing enteritis

what are clinical diseases of c. perfringens? (2)

• clostridial food poisoning

• necrotizing enteritis

which type of c. perfringens produces the beta toxin?

TYPE C

consuming what can lead to necrotizing enteritis?

undercooked pork w/ sweet potatoes (protect beta toxin)

what is necrotizing enteritis characterized by?

acute abdominal pain, vomiting, bloody diarrhea, ulceration of SI, perforation of the intestinal wall

can the enterotoxin from type A (c. perfringens) be destroyed by heat?

yes! @ 74 F

how should myositis and myonecrosis have to be treated?

AGGRESSIVELY; surgical debridement, high-dose penicillin

how is clostridial food poisoning managed?

rehydration

how does c. tetani look in comparison to other clostridium species? WHY?

drumstick, allows for motility

which state of c. tetani is extremely sensitive to ___?

vegetative, oxygen

what are the 2 vf of c. tetani?

• tetanolysin

• tetanospasmin

what is tetanolysin?

an oxygen-labile hemolysin

what is tetanospasmin?

a heat labile neurotoxin, A-B toxin

• produced during stationary and is released during cell lysis (toxin cleaved by protease)

what is the mech. behind tetanospasmin?

like C. botulinum (A-B toxin)

• toxin inside endosomal vesicles

  • neuron axon —> motor neuron soma

• endosome is acidified

  • (A-subunit) endopeptidase —> cleaves protein in trafficking/release of neurotransmitters

  • inactivation of proteins the regulate the release of glycine and GABA

• spastic paralysis

what is spastic paralysis?

unregulated excitatory synaptic activity in the motor neurons

what is most common disease of c. tetani?

generalized tetanus

how is general tetanus characterized?

sardonic smile - lockjaw/trismus

what is the gram staining of corynebacterium diphtheriae?

gram positive CLUB-shaped rods

what does the cell of Coryn. diphtheriae contain?

short chain mycolic acids

which selective media is used for C. diphtheriae?

Cysteine-Tellurite blood agar

what is the active vaccination program to eradicate C. diphtheriae?

TDaP/ DTaP

how is c. diphtheriae transmitted?

respiratory droplets or skin contact

what type of toxin is the diphtheriae toxin?

classic A-B toxin

what are the subunits for the A-B toxin in c. diphtheriae?

• A: catalytic region = active portion

• B: receptor binding & translocation region

how is the diphtheriae toxin introduced?

lysogenic phage

what receptor does the B subunit (c. diphtheriae) bind to?

herapin-binding epidermal growth factor

what does the mech of diphtheria toxin?

• A-B toxin in endosome

• endosome is acidified

• A unit leads to inactivation of protein EF- 2

  • ribosylation

  • leads to no protein synthesis

what regulates diphtheriae toxin synthesis and how?

diphtheriae toxin repressor (DTxR)

• high iron = no toxin production

• low iron = toxin production

what are clinical disease in c. diphtheriae?

• respiratory

• cutaneous

how is respiratory diphtheriae characterized?

• exudative pharyngitis

  • thick psuedomembrane covering tonsils, uvula, palate, nasopharnyx, larynx

how is cutaneous diphtheriae characterized?

papule development, which can evolve to chronic non healing ulcer (grayish membrane)