title: Exploiting Interkingdom Interactions for Development of Small-Molecule Inhibitors of Candida albicans Biofilm Formation.
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.
authors.affiliation: Biomerit Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: F Jerry
authors.initials: FJ
authors.lastname: Reen
authors.affiliation: Biomerit Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: John P
authors.initials: JP
authors.lastname: Phelan
authors.affiliation: Biomerit Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: Lorna
authors.initials: L
authors.lastname: Gallagher
authors.affiliation: Biomerit Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: David F
authors.initials: DF
authors.lastname: Woods
authors.affiliation: School of Chemistry and Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Shanahan
authors.affiliation: School of Chemistry and Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cano
authors.affiliation: School of Chemistry and Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: Eoin
authors.initials: E
authors.lastname: Ó Muimhneacháin
authors.affiliation: School of Chemistry and Analytical and Biological Chemistry Research Facility (ABCRF), University College Cork-National University of Ireland, Cork, Ireland.
authors.forename: Gerard P
authors.initials: GP
authors.lastname: McGlacken
authors.affiliation: Biomerit Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia f.ogara@ucc.ie.
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
mesh_terms: D042462:4-Quinolones / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000187:drug effects / Q000472:pathogenicity; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; C528166:2-heptyl-4-quinolone; D042462:4-Quinolones; C113620:ALS3 protein, Candida albicans; D000935:Antifungal Agents; C082909:ECE1 protein, Candida albicans; D005656:Fungal Proteins; C118102:HWP1 protein, Candida albicans; D008562:Membrane Glycoproteins; D015363:Quinolones; D054852:Small Molecule Libraries