2016
DOI: 10.1002/cbic.201600018
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The Antiadhesive Strategy in Crohn′s Disease: Orally Active Mannosides to Decolonize Pathogenic Escherichia coli from the Gut

Abstract: Blocking the adherence of bacteria to cells is an attractive complementary approach to current antibiotic treatments, which are faced with increasing resistance. This strategy has been particularly studied in the context of urinary tract infections (UTIs), in which the adhesion of pathogenic Escherichia coli strains to uroepithelial cells is prevented by blocking the FimH adhesin expressed at the tips of bacteria organelles called fimbriae. Recently, we extended the antiadhesive concept, showing that potent Fi… Show more

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Cited by 48 publications
(39 citation statements)
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“…A high inoculum of >10 9 CFU of the AIEC strain LF82 is given orally and mice are monitored for weight loss and fecal AIEC titers, and ileal tissues analyzed for bacterial burdens, AIEC colonization, and histopathology [68]. To test the efficacy of oral FimH antagonists in preventing Crohn's-like clinical signs and pathology in this mouse CEABAC10 model, mice were treated with 10 mg/kg of candidate compounds at 2 and 18 hpi and monitored over 3-4 days for weight loss, fecal and/or tissue titers, and ileal tissue histopathology and soluble mediators of inflammation [22, 69]. The FimH antagonists tested in these publications all showed efficacy in preventing Crohn's-like clinical signs and pathology, demonstrating the proof of concept that FimH antagonists could potentially be used to treat Crohn's symptoms in patients.…”
Section: Murine Animal Models Of Uti and Crohn's Disease (Cd)mentioning
confidence: 99%
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“…A high inoculum of >10 9 CFU of the AIEC strain LF82 is given orally and mice are monitored for weight loss and fecal AIEC titers, and ileal tissues analyzed for bacterial burdens, AIEC colonization, and histopathology [68]. To test the efficacy of oral FimH antagonists in preventing Crohn's-like clinical signs and pathology in this mouse CEABAC10 model, mice were treated with 10 mg/kg of candidate compounds at 2 and 18 hpi and monitored over 3-4 days for weight loss, fecal and/or tissue titers, and ileal tissue histopathology and soluble mediators of inflammation [22, 69]. The FimH antagonists tested in these publications all showed efficacy in preventing Crohn's-like clinical signs and pathology, demonstrating the proof of concept that FimH antagonists could potentially be used to treat Crohn's symptoms in patients.…”
Section: Murine Animal Models Of Uti and Crohn's Disease (Cd)mentioning
confidence: 99%
“…In another series targeting AIEC bacteria in CD, Gouin[22] designed a sulfur and carbon-linked heptyl O -mannoside (HM) derivatives (Fig. 7).…”
Section: Medicinal Chemistry Lead Optimization Of Drug-like Fimh Mmentioning
confidence: 99%
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“…To date, several strategies focused on AIEC growth control and reduction on intestinal mucosae are under study, such as the use of antibiotics, the attempt to block AIEC's adhesion ability by preventing the interaction between FimH and CEACAM6 [18,19], and the attempt to block AIEC's cell-invasion ability using the Gp96 chaperone or the OmpA trans-membrane proteins as targets [20,[42][43][44].…”
Section: In Vivo Predatory Activity Of B Bacteriovorus On Aiecmentioning
confidence: 99%
“…There are several examples in which the anti-adherence approach has been exploited successfully to design inhibitors of microbial adherence [6]. Some of these include glycoclusters capable of preventing lung infection caused by Pseudomonas aeruginosa [7] and glycoconjugates used in the treatment of conditions caused by pathogenic strains of Escherichia coli, such as Crohn's disease [8] and urinary tract infections [9,10]. The lectins involved in the adherence processes in these reports (Lec A and Lec B from P. auroginosa and Fim H from E. coli, respectively) have been extensively studied and detailed knowledge of their structure and binding specificities is available.…”
Section: Introductionmentioning
confidence: 99%