Fructooligosacharides Reduce Pseudomonas aeruginosa PAO1 Pathogenicity through Distinct Mechanisms

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.

Protein kinase C δ signaling is required for dietary prebiotic-induced strengthening of intestinal epithelial barrier function

“…However, our results do not preclude the possibility that prebiotics may also regulate the expression of EHEC virulence factors. In Pseudomonads, for example, FOS reduced the expression of exotoxin A and inhibited NF-κB activation25. Whether inulin and scFOS can regulate the expression of EHEC virulence factors remains an open question.…”

Implication of Fructans in Health: Immunomodulatory and Antioxidant Mechanisms

“…Additionally, they stimulate Lactobacillus and Bifidobacterium species to reduce the presence of pathogens in the gut and relieve constipation ( Table 1 ). Other fructans, including soluble gut oligosaccharides, mimic the sugar chains found in the glycoproteins and glycolipids of gut epithelial cells, thereby preventing the adhesion of pathogenic microorganisms [ 39 ] and exerting direct antimicrobial effects [ 40 ] ( Table 1 ).…”

Full Transcriptomic Response of Pseudomonas aeruginosa to an Inulin-Derived Fructooligosaccharide

“…Shown are means and standard deviations with n = 3-6; *P < 0.05 vs. WT. limited the formation of biofilm, impaired motility, and reduced the inflammatory response (Ortega-González et al, 2014). Although, inulin and FOS are structurally related oligosaccharides, they differ in chain length and both compounds can be used as a carbon and energy source for P. aeruginosa growth.…”

“…In addition to the bacterial growth promoting role of inulin and FOS, we reported that FOS inhibited bacterial growth and biofilm formation of P. aeruginosa PAO1 (Ortega-González et al, 2014). Additionally, both compounds caused opposing effects on bacterial motility.…”

“…Moreover, 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. We were also able to show that the reduction in cytokine secretion is due to a FOSmediated modulation of the NF-κβ signal transduction pathway (Ortega-González et al, 2014). To gain insight into the detailed molecular processes triggered by FOS and inulin, we report here results from RNA-seq studies.…”