ArticleThe Journal of biological chemistry2011
Functional diversity of heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli: differential enzymatic and immunological activities of LT1 (hLT) AND LT4 (pLT).
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
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- Dynamic interaction between Escherichia coli enterotoxins and bacteriocins.The FEBS journal · 2026Article
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- Construction of the ETECFinder database for the characterization of enterotoxigenicJournal of clinical microbiology · 2024Article
- Streptococcus mutans glutamate binding protein (GlnH) as antigen target for a mucosal anti-caries vaccine.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Article
- The evolutionary diversification of theFrontiers in microbiology · 2022Article
- Transcutaneous Administration of Dengue Vaccines.Viruses · 2020Article
- Preformulation Characterization and Stability Assessments of Secretory IgA Monoclonal Antibodies as Potential Candidates for Passive Immunization by Oral Administration.Journal of pharmaceutical sciences · 2020Article
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- Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein.Frontiers in immunology · 2017Article
- Diarrheagenic Escherichia coli.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2016Review
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- Maternal vaccination with a fimbrial tip adhesin and passive protection of neonatal mice against lethal human enterotoxigenic Escherichia coli challenge.Infection and immunity · 2015Article
- Allele variants of enterotoxigenic Escherichia coli heat-labile toxin are globally transmitted and associated with colonization factors.Journal of bacteriology · 2015Article
- Immunogenicity and in vitro and in vivo protective effects of antibodies targeting a recombinant form of the Streptococcus mutans P1 surface protein.Infection and immunity · 2014Article
- Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant.Frontiers in immunology · 2014Article
- Bacillus subtilis spores as vaccine adjuvants: further insights into the mechanisms of action.PloS one · 2014Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat-labile toxins (LTs) have ADP-ribosylation activity and induce the secretory diarrhea caused by enterotoxigenic Escherichia coli (ETEC) strains in different mammalian hosts. LTs also act as adjuvants following delivery via mucosal, parenteral, or transcutaneous routes. Previously we have shown that LT produced by human-derived ETEC strains encompass a group of 16 polymorphic variants, including the reference toxin (LT1 or hLT) produced by the H10407 strain and one variant that is found mainly among bacterial strains isolated from pigs (LT4 or pLT). Herein, we show that LT4 (with six polymorphic sites in the A (K4R, K213E, and N238D) and B (S4T, A46E, and E102K) subunits) displays differential in vitro toxicity and in vivo adjuvant activities compared with LT1. One in vitro generated LT mutant (LTK4R), in which the lysine at position 4 of the A subunit was replaced by arginine, showed most of the LT4 features with an ∼10-fold reduction of the cytotonic effects, ADP-ribosylation activity, and accumulation of intracellular cAMP in Y1 cells. Molecular dynamic studies of the A subunit showed that the K4R replacement reduces the N-terminal region flexibility and decreases the catalytic site crevice. Noticeably, LT4 showed a stronger Th1-biased adjuvant activity with regard to LT1, particularly concerning activation of cytotoxic CD8(+) T lymphocytes when delivered via the intranasal route. Our results further emphasize the relevance of LT polymorphism among human-derived ETEC strains that may impact both the pathogenicity of the bacterial strain and the use of these toxins as potential vaccine adjuvants.
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