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.

2016

October

Antimicrob Agents Chemother

Exploiting Interkingdom Interactions for Development of Small-Molecule Inhibitors of Candida albicans Biofilm Formation

Validated

Altmetric: 3 ()

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

60

10

5894

905

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

https://www.ncbi.nlm.nih.gov/pubmed/27458231

10.1128/AAC.00190-16