title: Functional and immunological characterization of a natural polymorphic variant of a heat-labile toxin (LT-I) produced by enterotoxigenic Escherichia coli (ETEC).
abstract: Heat-labile toxins (LT) encompass at least 16 natural polymorphic toxin variants expressed by wild-type enterotoxigenic Escherichia coli (ETEC) strains isolated from human beings, but only one specific form, produced by the reference ETEC H10407 strain (LT1), has been intensively studied either as a virulence-associated factor or as a mucosal/transcutaneous adjuvant. In the present study, we carried out a biological/immunological characterization of a natural LT variant (LT2) with four polymorphic sites at the A subunit (S190L, G196D, K213E, and S224T) and one at the B subunit (T75A). The results indicated that purified LT2, in comparison with LT1, displayed similar in vitro toxic activities (adenosine 3',5'-cyclic monophosphate accumulation) on mammalian cells and in vivo immunogenicity following delivery via the oral route. Nonetheless, the LT2 variant showed increased adjuvant action to ovalbumin when delivered to mice via the transcutaneous route while antibodies raised in mice immunized with LT2 displayed enhanced affinity and neutralization activity to LT1 and LT2. Taken together, the results indicate that the two most frequent LT polymorphic forms expressed by wild ETEC strains share similar biological features, but differ with regard to their immunological properties.
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Lasaro
authors.forename: Camila
authors.initials: C
authors.lastname: Mathias-Santos
authors.forename: Juliana F
authors.initials: JF
authors.lastname: Rodrigues
authors.forename: Luís C S
authors.initials: LC
authors.lastname: Ferreira
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000992:Antitoxins / Q000276:immunology; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D002460:Cell Line; D054307:Enterotoxigenic Escherichia coli / Q000502:physiology*; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology* / Q000633:toxicity*; D051379:Mice; D020125:Mutation, Missense; D009500:Neutralization Tests; D011110:Polymorphism, Genetic
chemical_list: D000907:Antibodies, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli