Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells
Date
2021-06-07
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Publisher
Springer
Abstract
Background: The classification of natural antimicrobials as potential antibiotic replacements is still hampered by the
absence of clear biological mechanisms behind their mode of action. This study investigated the mechanisms underlying
the anti-bacterial effect of a mixture of natural antimicrobials (maltodextrin, citric acid, sodium citrate, malic
acid, citrus extract and olive extract) against Campylobacter jejuni RC039, Salmonella enterica SE 10/72 and Clostridium
perfringens ATCC® 13124 invasion of Madin–Darby Canine Kidney cells (MDCK).
Results: Minimum sub-inhibitory concentrations were determined for Campylobacter jejuni (0.25%), Salmonella
enterica (0.50%) and Clostridium perfringens (0.50%) required for the in vitro infection assays with MDCK cells. The
antimicrobial mixture significantly reduced the virulence of all three pathogens towards MDCK cells and restored the
integrity of cellular tight junctions through increased transepithelial resistance (TEER) and higher expression levels
of ZO-1 (zonula occludens 1) and occludin. This study also identified the ERK (external regulated kinase) signalling
pathway as a key mechanism in blocking the pro-inflammatory cytokine production (IL-1β, IL-6, IL-8, TNF-α) in infected
cells. The reduction in hydrogen peroxide (
H2O2) production and release by infected MDCK cells, in the presence of
the antimicrobial mixture, was also associated with less tetrathionate formed by oxidation of thiosulphate (p < 0.0001).
Conclusion: The present study describes for the first time that mixtures of natural antimicrobials can prevent the formation
of substrates used by bacterial pathogens to grow and survive in anaerobic environments (e.g. tetrathionate).
Description
Publication history: Accepted - 1 June 2021; Published online - 7 June 2021
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Article
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Keywords
Campylobacter jejuni, Salmonella enterica, Clostridium perfringens, Natural antimicrobials, Hydrogen peroxide, ERK kinase, MDCK cells, Virulence
Citation
Balta, I., Marcu, A., Linton, M., Kelly, C., Gundogdu, O., Stef, L., Pet, I., Ward, P., Deshaies, M., Callaway, T., Sopharat, P., Gradisteanu-Pircalabioru, G. and Corcionivoschi, N. (2021) ‘Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells’, Gut Pathogens, 13(1). doi: 10.1186/s13099-021-00433-5.