Target intelligence / Profile preview

Heat-labile enterotoxin subunit A (LT-A) (LT-A)

Target
LT-A
Molecular classification
Enzyme [1], ADP-ribosyltransferase [3], Bacterial toxin [2]
01

Overview

Heat-labile enterotoxin subunit A (LT-A) is the enzymatic component of the heat-labile enterotoxin (LT) produced by enterotoxigenic Escherichia coli (ETEC) [1]. LT is an AB5-type toxin consisting of a single A subunit and a pentameric B subunit ring that facilitates cell entry [2]. Once inside host intestinal epithelial cells, the LT-A subunit is proteolytically cleaved into A1 and A2 fragments; the A1 fragment acts as an ADP-ribosyltransferase that targets the Gs alpha subunit of heterotrimeric G proteins [3]. This modification results in the constitutive activation of adenylate cyclase, leading to a massive increase in intracellular cyclic AMP (cAMP) levels [4]. The elevated cAMP triggers the opening of chloride channels and inhibits sodium absorption, causing the profuse watery diarrhea characteristic of ETEC infections [5]. LT-A is a primary target for the development of vaccines and antitoxin therapies aimed at preventing or treating traveler's diarrhea and childhood diarrhea in developing regions [6].

Other names
Heat-labile enterotoxin A chainLTALT subunit AEnterotoxin subunit alphaETEC LT-A
02

Mechanism of action

Neutralization of toxin activity by antibodies and competitive inhibition of ADP-ribosyltransferase activity [7, 9]

03

Biological functions

ADP-ribosylation [3]Signal transduction [4]Activation of adenylate cyclase [4]Ion transport regulation [5]
04

Disease associations

Infection [1]Traveler's diarrhea [5]Gastroenteritis [6]
05

Safety considerations

Severe dehydration [5]Toxicity as an adjuvant [10]Bell's palsy (intranasal administration) [10]
06

Interacting drugs

Dukoral (Oral cholera vaccine) [7]

4 more in the full profile.

07

Biomarkers

LT-specific IgG titers [8]LT-specific IgA titers [8]Intracellular cAMP levels [4]Fecal LT levels [1]

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