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