Escherichia coli heat-labile enterotoxin (LT)

Escherichia coli heat-labile enterotoxin (LT) is a multi-subunit bacterial protein toxin produced by enterotoxigenic E. coli (ETEC). It forms an AB5 multimeric structure, with a single A subunit harboring ADP-ribosyltransferase activity and a pentameric B subunit responsible for binding to ganglioside receptors on host epithelial cells[1][3]. Upon cell entry, the A subunit catalyzes ADP-ribosylation of Gsα, resulting in constitutive adenylate cyclase activation and excessive cAMP production, leading to chloride and water secretion and consequent diarrhea. LT shares structural and mechanistic similarity to cholera toxin[1][3]. Detoxified forms of LT (LTh) are used experimentally as potent mucosal adjuvants to enhance immune responses to co-administered antigens in vaccine research. The native toxin is not suitable for therapeutic use due to safety concerns but detoxified variants are under investigation as immunomodulators[2]. Important caveats: The name "Immune system modulation via detoxified Escherichia coli heat-labile enterotoxin LTh" is not a canonical target name; it refers to a bioactivity/therapeutic approach using a detoxified form of the LT toxin as an immunomodulatory agent. The canonical target is the toxin itself; LT is not a classical receptor, enzyme, or human protein, but functions as a bacterial toxin and experimental immune adjuvant. There is no specific "receptor" encoded in the human genome; instead, LT binds gangliosides on host cells and acts post-translationally via ADP-ribosylation[3]. “LTh” typically designates a detoxified mutant; canonical literature usually uses “LT” or specifies mutant forms.

Other names

E. coli heat-labile enterotoxinLTLT-I (Type I heat-labile enterotoxin)LT-IIaLT-IIbLT-IIc (Type II subtypes)ETEC heat-labile toxin

ADP-ribosylation of Gsα subunit of heterotrimeric G protein leading to activation of adenylate cyclase, elevated cAMP, and secretory diarrhea[2][1]. As an adjuvant: immune potentiation by stimulating specific immune responses (IgG2a, IgA, Th17)[2].