Fructooligosacharides reduce Pseudomonas aeruginosa PAO1 pathogenicity through distinct mechanisms

PLoS One. 2014 Jan 22;9(1):e85772. doi: 10.1371/journal.pone.0085772. eCollection 2014.

Abstract

Pseudomonas aeruginosa is ubiquitously present in the environment and acts as an opportunistic pathogen on humans, animals and plants. We report here the effects of the prebiotic polysaccharide inulin and its hydrolysed form FOS on this bacterium. FOS was found to inhibit bacterial growth of strain PAO1, while inulin did not affect growth rate or yield in a significant manner. Inulin stimulated biofilm formation, whereas a dramatic reduction of the biofilm formation was observed in the presence of FOS. Similar opposing effects were observed for bacterial motility, where FOS inhibited the swarming and twitching behaviour whereas inulin caused its stimulation. In co-cultures with eukaryotic cells (macrophages) FOS and, to a lesser extent, inulin reduced the secretion of the inflammatory cytokines IL-6, IL-10 and TNF-α. Western blot experiments indicated that the effects mediated by FOS in macrophages are associated with a decreased activation of the NF-κB pathway. Since FOS and inulin stimulate pathway activation in the absence of bacteria, the FOS mediated effect is likely to be of indirect nature, such as via a reduction of bacterial virulence. Further, this modulatory effect is observed also with the highly virulent ptxS mutated strain. Co-culture experiments of P. aeruginosa with IEC18 eukaryotic cells showed that FOS reduces the concentration of the major virulence factor, exotoxin A, suggesting that this is a possible mechanism for the reduction of pathogenicity. The potential of these compounds as components of antibacterial and anti-inflammatory cocktails is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP Ribose Transferases / metabolism
  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / metabolism
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Cytokines / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Exotoxins / metabolism
  • Female
  • Insulin / pharmacology
  • Interleukin-10 / metabolism
  • Interleukin-6 / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mutation
  • NF-kappa B / metabolism
  • Oligosaccharides / pharmacology*
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Virulence / genetics
  • Virulence Factors / metabolism

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Cytokines
  • DNA-Binding Proteins
  • Exotoxins
  • Insulin
  • Interleukin-6
  • NF-kappa B
  • Oligosaccharides
  • PtxS protein, Pseudomonas aeruginosa
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Virulence Factors
  • oligofructose
  • Interleukin-10
  • LysR protein, Bacteria
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa

Grant support

The authors acknowledge financial support from FEDER funds and Fondo Social Europeo through grants from the Spanish Ministry of Economy and Competitiveness (grants SAF2011-22922, SAF2011-22812) the Andalusian regional government Junta de Andalucía (grant CVI-7335) and the Centre of Networked Biomedical Research on Hepatic and Digestive Diseases (CIBERehd) which is funded by the Carlos III Health Institute and the Ramón Areces Foundation, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.