Title :

Evaluation of monovalent and multivalent iminosugars to modulate Candida albicans beta-1,2-mannosyltransferase activities

Author(s) :

Hurtaux, Thomas [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Sfihi-Loualia, Ghenima [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Brissonnet, Yoan [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Bouckaert, Julie [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Mallet, Jean-Maurice [Auteur]
Laboratoire des biomolécules [LBM UMR 7203]
Sendid, Boualem [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Delplace, Florence [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]
Fabre, Emeline [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Gouin Sebastien, G [Auteur]
Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation [CEISAM]
Guerardel, Yann [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF]

Journal title :

Carbohydrate research

Abbreviated title :

Carbohydr. Res.

Volume number :

429

Pages :

123-127

Publication date :

2016-06-24

ISSN :

0008-6215

English keyword(s) :

Mannosyltransferase
Iminosugars
Yeast
Inhibition
Multivalency

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

β-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in ...
Show more >β-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in immunocompromised patients. β-1,2-Mannosides are known to be involved in the pathogenic process and to elicit an immune response from the host. In C. albicans, the synthesis of β-mannosides is under the control of a family of nine genes coding for putative β-mannosyltransferases. Two of them, CaBmt1 and CaBmt3, have been shown to initiate and prime the elongation of the β-mannosides on the cell-wall mannan core. In the present study, we have assessed the modulating activities of monovalent and multivalent iminosugar analogs on these enzymes in order to control the enzymatic bio-synthesis of β-mannosides. We have identified a monovalent deoxynojirimycin (DNJ) derivative that inhibits the CaBmt1-catalyzed initiating activity, and mono-, tetra- and polyvalent deoxymannojirimycin (DMJ) that modulate the CaBmt1 activity toward the formation of a single major product. Analysis of the aggregating properties of the multivalent iminosugars showed their ability to elicit clusterization of both CaBmt1 and CaBmt3, without affecting their activity. These results suggest promising roles for multivalent iminosugars as controlling agents for the biosynthesis of β-1,2 mannosides and for monovalent DNJ derivative as a first target for the design of future β-mannosyltransferase inhibitors.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Inserm
Université de Lille
CHU Lille
CNRS

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Fungal associated invasive and inflammatory diseases

Submission date :

2019-03-01T15:15:58Z
2021-03-19T07:13:25Z