Exploiting interkingdom interactions for development of small-molecule inhibitors of Candida albicans biofilm formation

Reen, F. Jerry; Phelan, John P.; Gallagher, Lorna; Woods, David F.; Shanahan, Rachel M.; Cano, Rafael; Ó Muimhneacháin, Eoin; McGlacken, Gerard P.; O'Gara, Fergal

Exploiting interkingdom interactions for development of small-molecule inhibitors of Candida albicans biofilm formation

Files

11209_AAC_Reen_et_al_2016.pdf(1013.69 KB)

Accepted version

Date

2016-07-25

Authors

Reen, F. Jerry

Phelan, John P.

Gallagher, Lorna

Woods, David F.

Shanahan, Rachel M.

Cano, Rafael

Ó Muimhneacháin, Eoin

McGlacken, Gerard P.

O'Gara, Fergal

Publisher

American Society for Microbiology

Published Version

10.1128/AAC.00190-16

Abstract

A rapid decline in the development of new antimicrobial therapeutics has coincided with the emergence of new and more aggressive multidrug-resistant pathogens. Pathogens are protected from antibiotic activity by their ability to enter an aggregative biofilm state. Therefore, disrupting this process in pathogens is a key strategy for the development of next-generation antimicrobials. Here, we present a suite of compounds, based on the Pseudomonas aeruginosa 2-heptyl-4(1H)-quinolone (HHQ) core quinolone interkingdom signal structure, that exhibit noncytotoxic antibiofilm activity toward the fungal pathogen Candida albicans. In addition to providing new insights into what is a clinically important bacterium-fungus interaction, the capacity to modularize the functionality of the quinolone signals is an important advance in harnessing the therapeutic potential of signaling molecules in general. This provides a platform for the development of potent next-generation small-molecule therapeutics targeting clinically relevant fungal pathogens.

Keywords

4-Quinolones , Antifungal agents , Biofilms , Candida albicans , Cell Line , Fungal proteins , Gene expression regulation, fungal , Humans , Membrane glycoproteins , Pseudomonas aeruginosa , Quinolones , Small molecule libraries

Citation

Reen, F. J., Phelan, J. P., Gallagher, L., Woods, D. F., Shanahan, R. M., Cano, R., Ó Muimhneacháin, E., McGlacken, G. P. and O'Gara, F. (2016) ‘Exploiting interkingdom interactions for the development of small molecule inhibitors of Candida albicans biofilm formation’, Antimicrobial Agents and Chemotherapy, 60(10), pp. 5894-5905. doi: 10.1128/AAC.00190-16