Extracellular vesicles are conduits for E. coli heat-labile enterotoxin (LT) and the B-subunits of LT and cholera toxin in immune cell-to-cell communication

Bryson, Andreya; Gonzalez, Gabrielle de Paula Lopes; Al-Atoom, Nadia; Nashar, Nijad; Smith, Ja R'eika; Nashar, Toufic O.

doi:10.1016/j.micpath.2023.106038

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…LT act as virulence factors in enterotoxigenic bacteria ( 1 , 22 ) and consist of a subunit A (LTA) and five B subunits (LTB) ( 2 , 23 , 24 ). In fungi, there are no genes encoding LTB, but the genes for LTA are prevalent ( 4 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Homologs of bacterial heat-labile enterotoxin subunit A contribute to development, stress response, and virulence in filamentous entomopathogenic fungus Beauveria bassiana

Ding,

Wei,

Feng

et al. 2023

Front. Immunol.

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IntroductionEnterotoxigenic bacteria commonly excrete heat-labile enterotoxins (LT) as virulence factors that consist of one subunit A (LTA) and five B subunits (LTB). In fungi, there are a large number of genes encoding the homologs of LTA, but their biological roles remain largely unknown. MethodsIn this study, we identified 14 enterotoxin_A domain proteins in filamentous fungus B. bassiana in which five proteins were functionally characterized. ResultsFive proteins displayed diverse sub-cellular localizations but perform convergent functions in stress response, development, and virulence. The loss of five LTA genes resulted in significant reduction in conidial production, blastospore formation, and the increased sensitivity to oxidative and cell wall –perturbing stresses. The virulence of five disruptants was notably weakened as indicated by topical and intrahemocoel injection assays. Notably, the loss of these five proteins led to the significant changes in the carbohydrate profiles of cellular surface, which induced the enhanced host immune reactions of encapsulation and melanization. DiscussionThus, LTA proteins contribute to the fungus–host interaction via maintaining the carbohydrate profiles of cellular surface. This study expands our understanding of the enterotoxin_A domain proteins in fungal physiology and deepens mechanisms involved in the lifestyle of fungal insect pathogens.

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Section: Discussionmentioning

confidence: 99%

Homologs of bacterial heat-labile enterotoxin subunit A contribute to development, stress response, and virulence in filamentous entomopathogenic fungus Beauveria bassiana

Ding,

Wei,

Feng

et al. 2023

Front. Immunol.

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Cloning and characterization of an aerolysin gene from a marine pathogen Vibrio splendidus

Song,

Zhang

2024

Microbial Pathogenesis

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A Recombinant Shigella flexneri Strain Expressing ETEC Heat-Labile Enterotoxin B Subunit Shows Promise for Vaccine Development via OMVs

Salvador-Erro,

Pastor,

Gamazo

2024

IJMS

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Diarrheal diseases caused by Shigella and enterotoxigenic Escherichia coli (ETEC) are significant health burdens, especially in resource-limited regions with high child mortality. In response to the lack of licensed vaccines and rising antibiotic resistance for these pathogens, this study developed a recombinant Shigella flexneri strain with the novel incorporation of the eltb gene for the heat-labile enterotoxin B (LTB) subunit of ETEC directly into Shigella’s genome, enhancing stability and consistent production. This approach combines the immunogenic potential of LTB with the antigen delivery properties of S. flexneri outer membrane vesicles (OMVs), aiming to provide cross-protection against both bacterial pathogens in a stable, non-replicating vaccine platform. We confirmed successful expression through GM1-capture ELISA, achieving levels comparable to ETEC. Additionally, proteomic analysis verified that the isolated vesicles from the recombinant strains contain the LTB protein and the main outer membrane proteins and virulence factors from Shigella, including OmpA, OmpC, IcsA, SepA, and Ipa proteins, and increased expression of Slp and OmpX. Thus, our newly designed S. flexneri OMVs, engineered to carry ETEC’s LTB toxin, represent a promising strategy to be considered as a subunit vaccine candidate against S. flexneri and ETEC.

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Extracellular vesicles are conduits for E. coli heat-labile enterotoxin (LT) and the B-subunits of LT and cholera toxin in immune cell-to-cell communication

Cited by 3 publications

References 25 publications

Homologs of bacterial heat-labile enterotoxin subunit A contribute to development, stress response, and virulence in filamentous entomopathogenic fungus Beauveria bassiana

Homologs of bacterial heat-labile enterotoxin subunit A contribute to development, stress response, and virulence in filamentous entomopathogenic fungus Beauveria bassiana

Cloning and characterization of an aerolysin gene from a marine pathogen Vibrio splendidus

A Recombinant Shigella flexneri Strain Expressing ETEC Heat-Labile Enterotoxin B Subunit Shows Promise for Vaccine Development via OMVs

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