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Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms
- Source :
- Journal of Medicinal Chemistry, Journal of Medicinal Chemistry, American Chemical Society, 2019, 62 (17), pp.7722-7738. ⟨10.1021/acs.jmedchem.9b00481⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- International audience; Opportunistic Gram-negative Pseudomonas aeruginosa uses adhesins (e.g., LecA and LecB lectins, type VI pili and flagella) and iron to invade host cells with the formation of a biofilm, a thick barrier that protects bacteria from drugs and host immune system. Hindering iron uptake and disrupting adhesins’ function could be a relevant antipseudomonal strategy. To test this hypothesis, we designed an iron-chelating glycocluster incorporating a tetrahydroxamic acid and α-l-fucose bearing linker to interfere with both iron uptake and the glycan recognition process involving the LecB lectin. Iron depletion led to increased production of the siderophore pyoverdine by P. aeruginosa to counteract the loss of iron uptake, and strong biofilm inhibition was observed not only with the α-l-fucocluster (72%), but also with its α-d-manno (84%), and α-d-gluco (92%) counterparts used as negative controls. This unprecedented finding suggests that both LecB and biofilm inhibition are closely related to the presence of hydroxamic acid groups.
- Subjects :
- Siderophore
medicine.disease_cause
01 natural sciences
Pilus
Microbiology
03 medical and health sciences
chemistry.chemical_compound
540 Chemistry
Drug Discovery
medicine
[CHIM]Chemical Sciences
030304 developmental biology
0303 health sciences
Pyoverdine
biology
Pseudomonas aeruginosa
Biofilm
Lectin
biology.organism_classification
0104 chemical sciences
Bacterial adhesin
010404 medicinal & biomolecular chemistry
chemistry
biology.protein
570 Life sciences
Molecular Medicine
Bacteria
Subjects
Details
- Language :
- English
- ISSN :
- 00222623 and 15204804
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry, Journal of Medicinal Chemistry, American Chemical Society, 2019, 62 (17), pp.7722-7738. ⟨10.1021/acs.jmedchem.9b00481⟩
- Accession number :
- edsair.doi.dedup.....b24d2ecc3f50036e30f5a02abc05a55f