title: Harnessing Bacterial Signals for Suppression of Biofilm Formation in the Nosocomial Fungal PathogenAspergillus fumigatus.
abstract: Faced with the continued emergence of antibiotic resistance to all known classes of antibiotics, a paradigm shift in approaches toward antifungal therapeutics is required. Well characterized in a broad spectrum of bacterial and fungal pathogens, biofilms are a key factor in limiting the effectiveness of conventional antibiotics. Therefore, therapeutics such as small molecules that prevent or disrupt biofilm formation would render pathogens susceptible to clearance by existing drugs. This is the first report describing the effect of thePseudomonas aeruginosaalkylhydroxyquinolone interkingdom signal molecules 2-heptyl-3-hydroxy-4-quinolone and 2-heptyl-4-quinolone on biofilm formation in the important fungal pathogenAspergillus fumigatus. Decoration of the anthranilate ring on the quinolone framework resulted in significant changes in the capacity of these chemical messages to suppress biofilm formation. Addition of methoxy or methyl groups at the C5-C7 positions led to retention of anti-biofilm activity, in some cases dependent on the alkyl chain length at position C2. In contrast, halogenation at either the C3 or C6 positions led to loss of activity, with one notable exception. Microscopic staining provided key insights into the structural impact of the parent and modified molecules, identifying lead compounds for further development.
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: David F
authors.initials: DF
authors.lastname: Woods
authors.affiliation: Department of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork - National University of Ireland Cork, Ireland.
authors.forename: Rachel
authors.initials: R
authors.lastname: Shanahan
authors.affiliation: Department of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork - National University of Ireland Cork, Ireland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Cano
authors.affiliation: Department of Chemistry and Analytical and Biological Chemistry Research Facility, University College Cork - National University of Ireland Cork, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Clarke
authors.affiliation: Department of Chemistry and Analytical and Biological Chemistry Research Facility, 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 IrelandCork, Ireland; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, PerthWA, Australia.
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
keywords: Aspergillus fumigatus; HHQ; PQS; Pseudomonas aeruginosa; alkylhydroxyquinolone (AHQ); biofilm; interkingdom interactions