Plant-derived antimicrobials reduce Listeria monocytogenes virulence factors in vitro, and down-regulate expression of virulence genes

Listeria monocytogenes (LM) is a major foodborne pathogen causing septicemia, meningitis and death in humans. LM infection is preceded by its attachment to and invasion of human intestinal epithelium followed by systemic spread. The major virulence factors in LM include motility, hemolysin and lecithinase production. Reducing LM attachment to and invasion of host tissue and production of virulence factors could potentially control listeriosis in humans. This study investigated the efficacy of sub-inhibitory concentrations (SICs, concentrations not inhibiting bacterial growth) of three, generally regarded as safe (GRAS)-status, plant-derived antimicrobial compounds in reducing LM attachment to and invasion of human colon adenocarcinoma (Caco-2) and human brain microvascular endothelial cells (HBMEC). Additionally, the effect of these compounds on the aforementioned LM virulence factors was studied. The compounds and their respective SICs used relative to their MICs were trans-cinnamaldehyde (TC 0.50 mM, 0.75 mM with the MIC of 0.90 mM), carvacrol (CR 0.50 mM, 0.65 mM with the MIC of 0.75 mM), and thymol (TY 0.33 mM, 0.50 mM with the MIC of 0.60 mM). All three-plant antimicrobials reduced LM adhesion to and invasion of Caco-2 and HBMEC (p < 0.05). The compounds also decreased LM motility, hemolysin production and lecithinase activity (p < 0.05). Real-time PCR data revealed that TC, CR, and TY down-regulated the expression of LM virulence genes by > 3.0 folds compared to controls (p < 0.05). Results suggest that TC, CR, and TY could potentially be used to control LM infection; however, in vivo studies are necessary to validate these results.

► SICs of Trans-cinnamaldehyde (TC), Carvacrol (CR), and Thymol (TY) reduced motility, hemolysin and lecithinase production.
► SICs of TC, CR, and TY completely shut down LM invasion on HBMEC and reduced adhesion and invasion on Caco-2 cells significantly.
► SICs of TC, CR, and TY down regulated expression of major virulence genes.