Ortega-González Mercedes, Sánchez de Medina Fermín, Molina-Santiago Carlos, López-Posadas Rocío, Pacheco Daniel, Krell Tino, Martínez-Augustin Olga, Abdelali Daddaoua
Department of Biochemistry and Molecular Biology II, Centre of networked Biomedical Research about Hepatic and Digestive Diseases, School of Pharmacy, University of Granada, Granada, Spain.
Departments of Pharmacology, Centre of networked Biomedical Research about Hepatic and Digestive Diseases, School of Pharmacy, University of Granada, Granada, Spain.
PLoS One. 2014 Jan 22;9(1):e85772. doi: 10.1371/journal.pone.0085772. eCollection 2014.
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.
铜绿假单胞菌广泛存在于环境中,是人类、动物和植物的机会致病菌。我们在此报告益生元多糖菊粉及其水解形式低聚果糖(FOS)对这种细菌的影响。发现FOS可抑制PAO1菌株的细菌生长,而菊粉对生长速率或产量没有显著影响。菊粉刺激生物膜形成,而在FOS存在的情况下观察到生物膜形成显著减少。在细菌运动性方面也观察到类似的相反作用,FOS抑制群体游动和抽搐行为,而菊粉则刺激这种行为。在与真核细胞(巨噬细胞)的共培养中,FOS以及程度较轻的菊粉减少了炎性细胞因子IL-6、IL-10和TNF-α的分泌。蛋白质印迹实验表明,FOS在巨噬细胞中介导的作用与NF-κB途径的激活减少有关。由于FOS和菊粉在无细菌的情况下刺激途径激活,FOS介导的作用可能是间接性质的,例如通过降低细菌毒力。此外,在高毒力的ptxS突变菌株中也观察到这种调节作用。铜绿假单胞菌与IEC18真核细胞的共培养实验表明,FOS降低了主要毒力因子外毒素A的浓度,这表明这可能是致病性降低的一种机制。讨论了这些化合物作为抗菌和抗炎混合物成分的潜力。