Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions

The incidence of gastrointestinal illness attributable to <i>Salmonella enterica</i> serovar Typhimurium (ST) remains a concern for public health worldwide, as it can progress into systemic infections mediated by the type-three secretion system (T3SS), which allows for adherence and inva...

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Main Authors: Zabdiel Alvarado-Martinez, Zajeba Tabashsum, Arpita Aditya, Katherine Hshieh, Grace Suh, Matthew Wall, Aaron Scriba, George Sellers, Christa Canagarajah, Sarika Kapadia, Debabrata Biswas
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/6/1364
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author Zabdiel Alvarado-Martinez
Zajeba Tabashsum
Arpita Aditya
Katherine Hshieh
Grace Suh
Matthew Wall
Aaron Scriba
George Sellers
Christa Canagarajah
Sarika Kapadia
Debabrata Biswas
author_facet Zabdiel Alvarado-Martinez
Zajeba Tabashsum
Arpita Aditya
Katherine Hshieh
Grace Suh
Matthew Wall
Aaron Scriba
George Sellers
Christa Canagarajah
Sarika Kapadia
Debabrata Biswas
author_sort Zabdiel Alvarado-Martinez
collection DOAJ
description The incidence of gastrointestinal illness attributable to <i>Salmonella enterica</i> serovar Typhimurium (ST) remains a concern for public health worldwide, as it can progress into systemic infections mediated by the type-three secretion system (T3SS), which allows for adherence and invasion to intestinal epithelial cells. The current study evaluates the ability of gallic acid (GA), protocatechuic acid (PA), and vanillic acid (VA) to impair the adhesion and invasion abilities of ST to a human epithelial (INT-407) cell monolayer while also assessing their cytotoxicity. GA, PA, and VA inhibited detectable ST growth at specific concentrations but showed cytotoxicity against INT-407 cells (>20% reduction in viability) after 3 h of treatments. Adjusting the pH of the solutions had a neutralizing effect on cytotoxicity, though it did reduce their antimicrobial potency. Adhesion of ST was reduced significantly when the cells were treated with 4.0 mg/mL of VA, whereas invasion was reduced in all treatments, with GA requiring the lowest concentration (0.5 mg/mL). Relative gene expression of virulence genes after treatment with GA showed downregulation in the T3SS regulator and effector <i>hilA</i> and <i>sipA</i>, respectively. These findings suggest further use of phenolic acids in reducing the activity of key virulence factors critical during ST infection.
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spelling doaj.art-14ae08eb64694d44b78e70b464ee4da62024-03-27T13:57:10ZengMDPI AGMolecules1420-30492024-03-01296136410.3390/molecules29061364Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their InteractionsZabdiel Alvarado-Martinez0Zajeba Tabashsum1Arpita Aditya2Katherine Hshieh3Grace Suh4Matthew Wall5Aaron Scriba6George Sellers7Christa Canagarajah8Sarika Kapadia9Debabrata Biswas10Biological Sciences Program-Molecular and Cellular Biology, University of Maryland, College Park, MD 20742, USABiological Sciences Program-Molecular and Cellular Biology, University of Maryland, College Park, MD 20742, USADepartment of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USADepartment of Biology, University of Maryland, College Park, MD 20742, USABiological Sciences Program-Molecular and Cellular Biology, University of Maryland, College Park, MD 20742, USAThe incidence of gastrointestinal illness attributable to <i>Salmonella enterica</i> serovar Typhimurium (ST) remains a concern for public health worldwide, as it can progress into systemic infections mediated by the type-three secretion system (T3SS), which allows for adherence and invasion to intestinal epithelial cells. The current study evaluates the ability of gallic acid (GA), protocatechuic acid (PA), and vanillic acid (VA) to impair the adhesion and invasion abilities of ST to a human epithelial (INT-407) cell monolayer while also assessing their cytotoxicity. GA, PA, and VA inhibited detectable ST growth at specific concentrations but showed cytotoxicity against INT-407 cells (>20% reduction in viability) after 3 h of treatments. Adjusting the pH of the solutions had a neutralizing effect on cytotoxicity, though it did reduce their antimicrobial potency. Adhesion of ST was reduced significantly when the cells were treated with 4.0 mg/mL of VA, whereas invasion was reduced in all treatments, with GA requiring the lowest concentration (0.5 mg/mL). Relative gene expression of virulence genes after treatment with GA showed downregulation in the T3SS regulator and effector <i>hilA</i> and <i>sipA</i>, respectively. These findings suggest further use of phenolic acids in reducing the activity of key virulence factors critical during ST infection.https://www.mdpi.com/1420-3049/29/6/1364gallic acidprotocatechuic acidvanillic acid<i>Salmonella</i> TyphimuriumINT-407invasion
spellingShingle Zabdiel Alvarado-Martinez
Zajeba Tabashsum
Arpita Aditya
Katherine Hshieh
Grace Suh
Matthew Wall
Aaron Scriba
George Sellers
Christa Canagarajah
Sarika Kapadia
Debabrata Biswas
Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
Molecules
gallic acid
protocatechuic acid
vanillic acid
<i>Salmonella</i> Typhimurium
INT-407
invasion
title Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
title_full Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
title_fullStr Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
title_full_unstemmed Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
title_short Plant-Derived Phenolic Acids Limit the Pathogenesis of <i>Salmonella</i> Typhimurium and Protect Intestinal Epithelial Cells during Their Interactions
title_sort plant derived phenolic acids limit the pathogenesis of i salmonella i typhimurium and protect intestinal epithelial cells during their interactions
topic gallic acid
protocatechuic acid
vanillic acid
<i>Salmonella</i> Typhimurium
INT-407
invasion
url https://www.mdpi.com/1420-3049/29/6/1364
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