Iron Availability Increases the Pathogenic Potential of Salmonella Typhimurium and Other Enteric Pathogens at the Intestinal Epithelial Interface

• Published in: PloS one Vol. 7; no. 1; p. e29968
• Main Authors: Kortman, Guus A. M., Boleij, Annemarie, Swinkels, Dorine W., Tjalsma, Harold
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.01.2012; Public Library of Science (PLoS)
• Subjects: Adhesion; Adhesion tests; Bacteria; Bacterial Adhesion - drug effects; Bacterial Translocation - drug effects; Biological Availability; Biology; Caco-2 Cells; Chemokines; Citric acid; Citrobacter; Citrobacter freundii - growth & development; Citrobacter freundii - physiology; Commensals; Communicable diseases; Cytokines; Diarrhea; Dietary Supplements; Disease; Dose-Response Relationship, Drug; Enterococcus faecalis - growth & development; Enterococcus faecalis - physiology; Epithelial cells; Epithelium - metabolism; Epithelium - microbiology; Escherichia coli - growth & development; Escherichia coli - physiology; Ferric citrate; Ferric Compounds - pharmacology; Homeostasis; Host-Pathogen Interactions; Humans; Incubation; Infections; Infectious diseases; Inflammation; Intestinal microflora; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestine; Intestines - metabolism; Intestines - microbiology; Iron; Iron - metabolism; Iron compounds; Iron, Dietary - administration & dosage; Iron, Dietary - metabolism; Iron, Dietary - pharmacokinetics; Laboratories; Lactobacillus plantarum; Lactobacillus plantarum - growth & development; Lactobacillus plantarum - physiology; Medicine; Metabolic disorders; Microbiota (Symbiotic organisms); Mimicry; Mortality; Neutrophils; Pathogenic microorganisms; Pathogens; Plasmodium falciparum; Rodents; Salmonella; Salmonella food poisoning; Salmonella Typhimurium; Salmonella typhimurium - growth & development; Salmonella typhimurium - physiology; Studies; Translocation; Virulence; Virulence (Microbiology); Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0029968

Recent trials have questioned the safety of untargeted oral iron supplementation in developing regions. Excess of luminal iron could select for enteric pathogens at the expense of beneficial commensals in the human gut microflora, thereby increasing the incidence of infectious diseases. The objective of the current study was to determine the effect of high iron availability on virulence traits of prevalent enteric pathogens at the host-microbe interface. A panel of enteric bacteria was cultured under iron-limiting conditions and in the presence of increasing concentrations of ferric citrate to assess the effect on bacterial growth, epithelial adhesion, invasion, translocation and epithelial damage in vitro. Translocation and epithelial integrity experiments were performed using a transwell system in which Caco-2 cells were allowed to differentiate to a tight epithelial monolayer mimicking the intestinal epithelial barrier. Growth of Salmonella typhimurium and other enteric pathogens was increased in response to iron. Adhesion of S. typhimurium to epithelial cells markedly increased when these bacteria were pre-incubated with increasing iron concentration (P = 0.0001), whereas this was not the case for the non-pathogenic Lactobacillus plantarum (P = 0.42). Cellular invasion and epithelial translocation of S. typhimurium followed the trend of increased adhesion. Epithelial damage was increased upon incubation with S. typhimurium or Citrobacter freundii that were pre-incubated under iron-rich conditions. In conclusion, our data fit with the consensus that oral iron supplementation is not without risk as iron could, in addition to inducing pathogenic overgrowth, also increase the virulence of prevalent enteric pathogens.