Chalopin T, Brissonnet Y, Sivignon A, Deniaud D, Cremet L, Barnich N, Bouckaert J, Gouin S G
LUNAM Université, CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, UMR CNRS 6230, UFR des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Clermont Université, UMR 1071 Inserm/Université d'Auvergne, 63000 Clermont-Ferrand, France and INRA, Unité Sous Contrat 2018, 63000 Clermont-Ferrand, France.
Org Biomol Chem. 2015 Dec 14;13(46):11369-75. doi: 10.1039/c5ob01581b.
Mono- and polyvalent ligands with strong affinities for the mannose-binding adhesin FimH were synthesised, and their anti-adhesive properties against ten E. coli strains were compared in two cell-based assays. The compounds were assessed against the non-pathogenic E. coli K12 and nine strains isolated by coproculture or from patients with osteoarticular infections (OIs), Crohn's disease (CD) and urinary tract infections (UTIs). The results showed that the compounds could inhibit the whole set of bacterial strains but with marked differences in terms of effective concentrations. The relative inhibitory potency of the monovalent compounds was also conserved for the ten strains and in the two assays. These results clearly suggest that a potent monovalent anti-adhesive assessed on a single E. coli strain will probably be effective on a broad range of strains and may treat diverse E. coli infections (OIs, CD and UTIs). In contrast, the polyvalent compounds showed a significant strain-dependancy in preventing E. coli attachment to intestinal cells. The multivalent antiadhesive effect may therefore vary depending on the E. coli strain tested.
合成了对甘露糖结合粘附素FimH具有强亲和力的单价和多价配体，并在两种基于细胞的试验中比较了它们对十种大肠杆菌菌株的抗粘附特性。这些化合物针对非致病性大肠杆菌K12以及通过共培养或从骨关节炎感染（OI）、克罗恩病（CD）和尿路感染（UTI）患者中分离出的九种菌株进行了评估。结果表明，这些化合物可以抑制所有测试的细菌菌株，但在有效浓度方面存在显著差异。单价化合物的相对抑制效力在十种菌株以及两种试验中也保持一致。这些结果清楚地表明，在单一大肠杆菌菌株上评估的强效单价抗粘附剂可能对广泛的菌株有效，并可能治疗多种大肠杆菌感染（OI、CD和UTI）。相比之下，多价化合物在防止大肠杆菌附着于肠道细胞方面表现出显著的菌株依赖性。因此，多价抗粘附效果可能因所测试的大肠杆菌菌株而异。
