Peer-Reviewed Journal Details
Mandatory Fields
Reen, F. J.,Phelan, J. P.,Gallagher, L.,Woods, D. F.,Shanahan, R. M.,Cano, R.,O. Muimhneachain E,McGlacken, G. P.,O'Gara, F.
Antimicrob Agents Chemother
Exploiting Interkingdom Interactions for Development of Small-Molecule Inhibitors of Candida albicans Biofilm Formation
Optional Fields
4-Quinolones/chemistry/pharmacology Antifungal Agents/chemistry/*pharmacology Biofilms/drug effects Candida albicans/*drug effects/physiology Cell Line Fungal Proteins/genetics Gene Expression Regulation, Fungal/drug effects Humans Membrane Glycoproteins/genetics Pseudomonas aeruginosa/*chemistry/drug effects/pathogenicity Quinolones/chemistry/pharmacology Small Molecule Libraries/chemistry/*pharmacology
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.
1098-6596 (Electronic) 00
Grant Details