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

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