title: Iron-induced virulence of Salmonella enterica serovar typhimurium at the intestinal epithelial interface can be suppressed by carvacrol.
abstract: Oral iron therapy can increase the abundance of bacterial pathogens, e.g., Salmonella spp., in the large intestine of African children. Carvacrol is a natural compound with antimicrobial activity against various intestinal bacterial pathogens, among which is the highly prevalent Salmonella enterica serovar Typhimurium. This study aimed to explore a presumed interaction between carvacrol and bacterial iron handling and to assess the potential of carvacrol in preventing the increase of bacterial pathogenicity during high iron availability. S. Typhimurium was cultured with increasing concentrations of iron and carvacrol to study the effects of these combined interventions on growth, adhesion to intestinal epithelial cells, and iron uptake/influx in both bacterial and epithelial cells. In addition, the ability of carvacrol to remove iron from the high-affinity ligand transferrin and an Fe-dye complex was examined. Carvacrol retarded growth of S. Typhimurium at all iron conditions. Furthermore, iron-induced epithelial adhesion was effectively reduced by carvacrol at high iron concentrations. The reduction of growth and virulence by carvacrol was not paralleled by a change in iron uptake or influx into S. Typhimurium. In contrast, bioavailability of iron for epithelial cells was moderately decreased under these conditions. Further, carvacrol was shown to lack the properties of an iron binding molecule; however, it was able to weaken iron-ligand interactions by which it may possibly interfere with bacterial virulence. In conclusion, our in vitro data suggest that carvacrol has the potential to serve as a novel dietary supplement to prevent pathogenic overgrowth and colonization in the large intestine during oral iron therapy.
authors.affiliation: Department of Laboratory Medicine, Nijmegen Institute for Infection, Inflammation, and Immunity (N4i), and Institute for Genetic and Metabolic Disease (IGMD) of the Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Guus A M
authors.initials: GA
authors.lastname: Kortman
authors.forename: Rian W H M
authors.initials: RW
authors.lastname: Roelofs
authors.forename: Dorine W
authors.initials: DW
authors.lastname: Swinkels
authors.forename: Marien I
authors.initials: MI
authors.lastname: de Jonge
authors.forename: Sara A
authors.initials: SA
authors.lastname: Burt
authors.forename: Harold
authors.initials: H
authors.lastname: Tjalsma
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D018938:Caco-2 Cells / Q000382:microbiology; D000081007:Cymenes; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology*; D007501:Iron / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000472:pathogenicity; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000081007:Cymenes; D005290:Ferric Compounds; D039821:Monoterpenes; C025314:ferric citrate; C073316:carvacrol; D007501:Iron