Mechanisms of Action and Cell Death Associated with Clostridium perfringens Toxins

Mauricio A Navarro1, Bruce A McClane2, Francisco A Uzal3

  • 1California Animal Health and Food Safety Laboratory, San Bernardino Branch, School of Veterinary Medicine, University of California-Davis, San Bernardino, CA 92408, USA. mnavarrob@ucdavis.edu.

Toxins
|May 23, 2018
PubMed

Insights

Clostridium perfringens toxins cause various infections. This study details major toxins like alpha toxin and enterotoxin (CPE), their roles in diseases, and cell death mechanisms.

Area of Science:

  • Microbiology
  • Toxicology
  • Pathogenesis

Background:

  • Clostridium perfringens produces diverse protein toxins.
  • These toxins cause histotoxic, neurologic, and intestinal infections in humans and animals.
  • Key toxins include alpha (CPA), beta (CPB), epsilon (ETX), iota (ITX), enterotoxin (CPE), and NetB.

Purpose of the Study:

  • To review the roles of major Clostridium perfringens toxins in human and animal diseases.
  • To elucidate the mechanisms of host-toxin interactions and resulting cell death.

Main Methods:

  • Literature review of Clostridium perfringens toxins and their associated diseases.
  • Analysis of host-toxin interactions at the cellular level.
  • Examination of molecular mechanisms of cell death.

Main Results:

  • CPA is linked to gas gangrene in humans; CPB causes necrotizing enteritis.
  • ETX is key in sheep/goat enterotoxemia; CPE causes human food poisoning.
  • NetB is responsible for necrotic enteritis in chickens.

Conclusions:

  • Clostridium perfringens toxins initiate disease via host cell plasma membrane interactions.
  • Toxin-induced cell death involves apoptosis, necrosis, and/or necroptosis.
  • Understanding these toxins is crucial for disease prevention and treatment.

Related Concept Videos

Depolarizing Blockers: Mechanism of Action01:28

Depolarizing Blockers: Mechanism of Action

Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
2.9K
Local Anesthetics: Mechanism of Action01:23

Local Anesthetics: Mechanism of Action

Local anesthetics (LAs) block sensory and motor impulses by inhibiting the sodium channels on the nerve cell membranes. This induces temporary loss of sensation, relieving pain in a specific body area.
Local anesthetics are amphiphilic molecules consisting of a hydrophobic aromatic part linked to a hydrophilic group by an ester or amide linkage. They are weak bases and are usually available as salts, which increases their solubility and stability. Once administered, LAs exist in the body either...
3.4K
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
2.7K
Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action01:17

Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action

Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
2.9K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.6K
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
10.2K