Mixtures of natural antimicrobials can reduce Campylobacter jejuni, Salmonella enterica and Clostridium perfringens infections and cellular inflammatory response in MDCK cells

Gut Pathogens

Patrick Ward¹  Phittawat Sopharat¹  Myriam Deshaies¹  Todd Callaway²  Ozan Gundogdu³  Adela Marcu⁴  Ioan Pet⁴  Lavinia Stef⁴  Carmel Kelly⁵  Mark Linton⁵  Igori Balta⁶  Nicolae Corcionivoschi⁶  Gratiela Gradisteanu-Pircalabioru⁷ 

[1] Auranta, Nova UCD, Belfield, Dublin, Ireland;Department of Animal and Dairy Science, University of Georgia, Athens, GA, USA;Department of Infection Biology, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT, London, UK;Faculty of Bioengineering of Animal Resources, Banat University of Agricultural Sciences and Veterinary Medicine-King Michael I of Romania, 300645, Timisoara, Romania;Food Microbiology, Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, 18a Newforge Lane, BT9 5PX, Belfast, Northern Ireland, UK;Food Microbiology, Bacteriology Branch, Veterinary Sciences Division, Agri-Food and Biosciences Institute, 18a Newforge Lane, BT9 5PX, Belfast, Northern Ireland, UK;Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 400372, Cluj-Napoca, Romania;Faculty of Bioengineering of Animal Resources, Banat University of Agricultural Sciences and Veterinary Medicine-King Michael I of Romania, 300645, Timisoara, Romania;Research Institute of University of Bucharest (ICUB), 300645, Bucharest, Romania;

关键词: C. jejuni;    S. enterica;    C. perfringens;    Natural antimicrobials;    Hydrogen peroxide;    ERK kinase;    MDCK cells;    Virulence;   

DOI  :  10.1186/s13099-021-00433-5

来源: Springer

【 摘 要 】

BackgroundThe 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).ResultsMinimum 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).ConclusionThe 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). Moreover, we provide further insights into pathogen invasion mechanisms through restoration of cellular structures and describe their ability to block the ERK–MAPK kinase pathway responsible for inflammatory cytokine release

【 授权许可】

CC BY