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.

2-Heptyl-4-Quinolone, a Precursor of the Pseudomonas Quinolone Signal Molecule, Modulates Swarming Motility in Pseudomonas aeruginosa

“…on May 9, 2018 by guest http://jb.asm.org/ or significant changes in phz gene expression in the wild type versus the ⌬sadC ⌬roeA double mutant (data not shown). In sum, we believe our study supplements the growing literature demonstrating signaling and regulatory properties of HHQ and PCA (12,15,43,52). This report originated from investigating the effects of arginine on swarming motility.…”

“…Therefore, we propose that while both PQS and HHQ contribute to full expression of the phz genes, the HHQ-mediated expression of these genes is essential for the observed swarming phenotype. And although not explored here, we recognize that other quinolone molecules are produced via HHQ, such as 4Q-N-oxides (12,15,43,52), which may also contribute to the expression of phz genes and/or repressing swarming motility on arginine. Deducing the effects of other quinolone molecules will be a topic for future investigation.…”

Inhibition of co-colonizing cystic fibrosis-associated pathogens by Pseudomonas aeruginosa and Burkholderia multivorans

“…aeruginosa has previously been shown to inhibit the growth of Candida during co-colonization. P. aeruginosa repressed C. albicans biofilm formation in a QS-dependent (Reen et al, 2011) and QS-independent (Holcombe et al, 2010) manner. In addition, while Ps.…”

“…In particular, the Ps. aeruginosa quinolone signal PQS and its biological precursor HHQ have been shown to directly antagonize a broad spectrum of CF-associated bacterial and fungal pathogens (Reen et al, 2011(Reen et al, , 2012; as well as targeting host-specific factors involved in infection (Kim et al, 2010a;b;Legendre et al, 2012). PQS has also been shown to control the expression of genes associated with iron scavenging and can itself act as an iron trap (Bredenbruch et al, 2006;Diggle et al, 2007).…”

The Stringent Response Modulates 4-Hydroxy-2-Alkylquinoline Biosynthesis and Quorum-Sensing Hierarchy in Pseudomonas aeruginosa

“…These molecules have diverse biological properties and have been implicated in interspecies interactions and competition (10)(11)(12), iron chelation (13,14), colony morphology (15), biofilm formation (16), and virulence (17)(18)(19). PQS is the bestcharacterized HAQ molecule, which functions as the third quorum-sensing signal in P. aeruginosa cell-cell communication (20,21).…”