Lecture 4.3

Clostridia

Gram +

Spore forming

Obligate anaerobic

Rod-shaped

Catalase and oxidase -

All form toxins

Flagellated and motile except C perfringens

Rapid growth

Do not exhibit hemolysis on blood agar except C tetani and C perfringens (sheep’s blood only)

Clostridia toxins

Tetanus and botulinum

Proteases that cleave SNARE proteins involved in neurotransmission

Clostridioides difficult (C. Diff) virulence factors

Toxin A

Toxin B

C. Diff Toxin A

Enterotoxin

Recruits neutrophils

Stimulates cytokine release in the ileum

Disrupts the tight junctions in the intestinal tract

Increases permeability and fluid secretion

C. Diff Toxin B

Cytotoxin

Disrupts the cytoskeleton by depolarizing actin filaments

GI mucosal cell death and pseudomembrane formation

How do C. Diff toxins A and B interact?

Synergistically

Destroy cytoskeleton of GI cells

Cause acute diarrhea and pseudomembranous colitis

Clostridium tetani

Tetanospasmin functions as a protease that cleaves the SNARE proteins, blocks glycine and GABA realease by inhibitory neurons into the NMJ, which leads to uncontrolled muscle contraction

Works in the spinal cord (renshaw cell)

Spasms and muscle contraction

Tetanospasmin

Heat liable neurotoxin

Functions as a protease

Renshaw cells

Inhibitory spinal cord interneuron

Spasms/muscle contractions

Rigidity

Lockjaw

Risus sardonicus ( raised eyebrow and open grin)

Spastic paralysis

Opisthotonos (spasms of spinal extensors)

Botulinum toxin

Cleavage of SNARE protein inhibits the release of ACh into the NMJ, preventing muscle contraction And leading to botulism

Botulism

Descending flaccid paralysis

Food borne botulism

Undercooked food

Canned food: aerobic environment promotes growth

Watch for multiple sick adults after a meal

Infant botulism (spores)

70% of total cases

Ingestion of spores (contaminated honey) leads to growth in infants intestine

Cause floppy baby syndrome and constipation

Can result in infant death

Wound botulism

Rare, bacterial growth

Infection with C. Botulism spore

Inhalation botulism

Rare

Releasing C. Botulism spores into the environment

Is a potential bioterrorism weapon

Neonatal tetanus

It occurs when a newborn is infected with the bacterium through an unsealed umbilical stump, usually due to no sterile delivery practices

Clostridium perfringens

Food poisoning

Gas gangrene

Food poisoning

Consuming undercooked meats contaminated with C perfringens

Spore contaminated food is cooked but left to stand too long at less than 60 degrees C leading to spore germination, vegetative bacteria, periodical heat liable enterotoxin that perforated the intestinal epithelium and leads to produce watery diarrhea

Late onset (10-12 hrs) watery diarrhea

Abdominal cramping and watery diarrhea without fever or vomiting

Self limiting and usually resolves within 24 hours

Gas gangrene (clostridial myonecrosis)

Very severe form of soft tissue infection with C perfringens

Via wound infection following localized trauma

Favorable environment for anaerobic growth

Alpha toxin = phospholipase (lecithinase) that lyses cells

Destroys muscle tissue and causes extensive hemolysis

Phospholipase that acts on lecithin

Degrades phospholipids in cell membranes

Leads to muscle breakdown (myonecrosis)