This is in accordance with previous investigations that have examined supernatants from bacterial strains found in the respiratory and gastrointestinal tracts, which identified P. aeruginosa supernatant to have inhibitory properties against A. fumigatus (Yadav et al., 2005). The main antimycotic agent was shown to be pyocyanin and 1-hydroxyphenazine, which Selleck Trametinib are controlled by multiple quorum-sensing systems (Kerr et al., 1999). These networks of genes may play an important role in controlling the interactions between P. aeruginosa with A. fumigatus. It was reported that both HSL molecules and lipopolysaccharides

influence C. albicans morphology and biofilm formation, and that signalling between these two CF pathogens is bidirectional, with farnesol inhibiting the swarming ability of P. aeruginosa (McAlester et al., 2008; Bandara et al., 2010a). Further work is required to determine whether bidirectional chemical interactions exist between P. aeruginosa and A. fumigatus, as no quorum-sensing molecule has been identified as yet for A. fumigatus. This is indeed likely as autoregulatory molecules

have been identified from a range of fungal pathogens, including C. albicans (farnesol and tyrosol), Saccharomyces cerevisiae (tryptophol and phenylethylalcohol), Cryptococcus neoformans (11-mer) and Penicillium paneum (octen-3-ol) (Hornby et al., 2001; Chen et al., 2004; Chitarra et al., 2004; Alem et al., 2006; Lee et al., 2007). The interaction between P. aeruginosa Protein Tyrosine Kinase inhibitor with fungi has been reported, with C. albicans exposure to P. aeruginosa quorum-sensing molecules inhibiting filamentation (Hogan & Kolter, 2002; Hogan et al., 2004; Shirtliff et al., 2009; Holcombe et al., 2010). Our study reported that the deletion of the principal quorum-sensing

networks of P. aeruginosa (LasIR) significantly reduced the capacity for A. fumigatus to form hyphae and undergo biofilm development. Given that a similar inhibitory effect was observed Flavopiridol (Alvocidib) both through direct and through indirect interaction suggested that the release of small heat-stable molecule was responsible for the inhibition, which was confirmed as both filtered and heat-killed supernatants also elicited a biological effect. However, similar inhibition profiles were observed for both LasI and LasR, the former of which is unable to synthesize HSL. These data indicate that molecules, other than or in addition to, HSLs may play a role in modulating A. fumigatus filamentation. Hogan et al. (2004) demonstrated that 3OC12-HSL inhibited the dimorphic switching of C. albicans at a range of concentrations, whereas the smaller molecule C4-HSL had no effect on C. albicans (Hogan et al., 2004). The authors tested 10 different structurally related compounds to assess their ability to inhibit the filamentation of C. albicans, of which four (3OC12-HSL, C12-HSL, dodecanol and farnesol) inhibited the dimorphic switching of C. albicans.