title: The Pseudomonas quinolone signal (PQS), and its precursor HHQ, modulate interspecies and interkingdom behaviour.
abstract: The Pseudomonas quinolone signal (PQS), and its precursor 2-heptyl-4-quinolone (HHQ), play a key role in coordinating virulence in the important cystic fibrosis pathogen Pseudomonas aeruginosa. The discovery of HHQ analogues in Burkholderia and other microorganisms led us to investigate the possibility that these compounds can influence interspecies behaviour. We found that surface-associated phenotypes were repressed in Gram-positive and Gram-negative bacteria as well as in pathogenic yeast in response to PQS and HHQ. Motility was repressed in a broad range of bacteria, while biofilm formation in Bacillus subtilis and Candida albicans was repressed in the presence of HHQ, though initial adhesion was unaffected. Furthermore, HHQ exhibited potent bacteriostatic activity against several Gram-negative bacteria, including pathogenic Vibrio vulnificus. Structure-function analysis using synthetic analogues provided an insight into the molecular properties that underpin the ability of these compounds to influence microbial behaviour, revealing the alkyl chain to be fundamental. Defining the influence of these molecules on microbial-eukaryotic-host interactions will facilitate future therapeutic strategies which seek to combat microorganisms that are recalcitrant to conventional antimicrobial agents.
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, University College Cork, Ireland.
authors.forename: F Jerry
authors.initials: FJ
authors.lastname: Reen
authors.forename: Marlies J
authors.initials: MJ
authors.lastname: Mooij
authors.forename: Lucy J
authors.initials: LJ
authors.lastname: Holcombe
authors.forename: Christina M
authors.initials: CM
authors.lastname: McSweeney
authors.forename: Gerard P
authors.initials: GP
authors.lastname: McGlacken
authors.forename: John P
authors.initials: JP
authors.lastname: Morrissey
authors.forename: Fergal
authors.initials: F
authors.lastname: O'Gara
mesh_terms: D042462:4-Quinolones / Q000494:pharmacology*; D000898:Antibiosis; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000472:pathogenicity; D015363:Quinolones / Q000494:pharmacology*; D015398:Signal Transduction; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014774:Virulence
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; C528166:2-heptyl-4-quinolone; D042462:4-Quinolones; D015363:Quinolones