Peer-Reviewed Journal Details
Mandatory Fields
Reen, FJ;Phelan, JP;Gallagher, L;Woods, DF;Shanahan, RM;Cano, R;Muimhneachain, EO;McGlacken, GP;O'Gara, F
Antimicrobial Agents and Chemotherapy
Exploiting Interkingdom Interactions for Development of Small-Molecule Inhibitors of Candida albicans Biofilm Formation
Optional Fields
4-Quinolones Antifungal agents Biofilms Candida albicans Cell Line Fungal proteins Gene expression regulation, fungal Humans Membrane glycoproteins Pseudomonas aeruginosa Quinolones Small molecule libraries
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.
Grant Details