Overview
Exotoxins are soluble proteins produced by bacteria and secreted into the extracellular environment, where they exert specific and often potent effects on host cells. They act enzymatically or by forming pores, disrupting normal cellular functions and contributing to the pathology of bacterial infections.
Explanation
Unlike endotoxin, which is an integral part of the Gram-negative outer membrane, exotoxins are secreted proteins that can be produced by Gram-positive and Gram-negative bacteria. Many are heat-labile and highly immunogenic; antibodies (antitoxins) can neutralise their activity, and chemically inactivated exotoxins serve as successful vaccine components. Structurally they are classified into three major groups. A-B toxins consist of an enzymatically active A subunit and a binding B subunit; examples include diphtheria toxin, which ADP-ribosylates elongation factor 2 and halts protein synthesis, and cholera toxin, which activates adenylate cyclase to cause secretory diarrhoea. Membrane-disrupting toxins form pores or enzymatically degrade cell membranes; haemolysins, streptolysin O and phospholipase C are examples. Superantigens, such as staphylococcal toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxins, non-specifically activate large numbers of T cells, leading to massive cytokine release and systemic effects. Exotoxins are often encoded by mobile genetic elements, including plasmids and bacteriophages, facilitating horizontal transfer. Detection involves immunoassays, cell culture assays or genetic tests, and treatment may require antitoxin administration in addition to antibiotics.
Types and clinical impact
Botulinum neurotoxins produced by Clostridium botulinum cleave SNARE proteins in motor neurons, leading to flaccid paralysis in botulism. Tetanospasmin from Clostridium tetani blocks inhibitory neurotransmitter release, causing spastic paralysis in tetanus. The diphtheria toxin from Corynebacterium diphtheriae is responsible for the necrotising pseudomembrane of diphtheria. Bacillus anthracis secretes protective antigen, lethal factor and oedema factor, which collectively disrupt immune signalling and cause the manifestations of anthrax. Staphylococcal enterotoxins and toxic shock syndrome toxin-1 act as superantigens leading to food poisoning and toxic shock syndrome. Pertussis toxin from Bordetella pertussis modifies G proteins and contributes to the paroxysmal cough of whooping cough. These examples illustrate the variety of exotoxin mechanisms and their role in bacterial diseases.
Exotoxins are among the most powerful biologically produced substances, yet their protein nature allows inactivation and exploitation for vaccines. Understanding their structure and mode of action informs clinical management and public health interventions.
Related Terms: Endotoxin, Enterotoxin, Toxoid, AB toxin, Neurotoxin