Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms

Taouai, Marwa; Chakroun, Khouloud; Sommer, Roman; Michaud, Gaelle; Giacalone, David; Ben Maaouia, Mohamed Amine; Vallin-Butruille, Aurélie; Mathiron, David; Abidi, Rym; Darbre, Tamis; Cragg, Peter J.; Mullié, Catherine; Reymond, Jean-Louis; O’Toole, George A.; Benazza, Mohammed (2019). Glycocluster Tetrahydroxamic Acids Exhibiting Unprecedented Inhibition of Pseudomonas aeruginosa Biofilms. Journal of medicinal chemistry, 62(17), pp. 7722-7738. American Chemical Society 10.1021/acs.jmedchem.9b00481

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Michaud, Gaëlle; Darbre, Tamis and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0022-2623

Publisher:

American Chemical Society

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

24 Jan 2020 15:00

Last Modified:

24 Jan 2020 15:00

Publisher DOI:

10.1021/acs.jmedchem.9b00481

PubMed ID:

31449405

BORIS DOI:

10.7892/boris.138517

URI:

https://boris.unibe.ch/id/eprint/138517

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