Pseudomonas aeruginosa causes infections in a wide variety of hosts and is the leading cause of mortality in cystic fibrosis (CF) patients. Although most clinical isolates of P. aeruginosa share common virulence determinants, it is known that strains evolve and change phenotypically during CF lung infections. These changes can include alterations in the levels of N-acyl homoserine lactones (HSLs), which are secreted signal molecules. In the CF lung, fungi, especially Candida albicans and Aspergillus fumigatus, may coexist with P. aeruginosa but the implications for disease are not known. Recent studies have established that signalling can occur between P. aeruginosa and C. albicans, with the bacterial molecule 3-oxo-C12HSL affecting Candida morphology, and the fungal metabolite farnesol reducing levels of the Pseudomonas quinolone signal and pyocyanin in Pseudomonas. Whether these interactions are common and typical in clinical strains of P. aeruginosa was addressed using CF isolates that produced varied levels of HSLs. It was found that, whereas some clinical P. aeruginosa strains affected C. albicans morphology, others did not. This correlated closely with the amounts of 3-oxo-C12HSL produced by the isolates. Furthermore, it was established that signalling is bidirectional and that the C. albicans molecule farnesol inhibits swarming motility in P. aeruginosa CF strains. This work demonstrates that clinical isolates of these opportunistic pathogens can interact in strain-specific ways via secreted signals and illustrates the importance of studying these interactions to fully understand the microbial contribution to disease in polymicrobial infections.

Signal-mediated interactions between the human opportunistic pathogens Pseudomonas aeruginosa and Candida albicans affect virulence traits in both organisms. Phenotypic studies revealed that bacterial supernatant from four P. aeruginosa strains strongly reduced the ability of C. albicans to form biofilms on silicone. This was largely a consequence of inhibition of biofilm maturation, a phenomenon also observed with supernatant prepared from non-clinical bacterial species. The effects of supernatant on biofilm formation were not mediated via interference with the yeast-hyphal morphological switch and occurred regardless of the level of homoserine lactone (HSL) produced, indicating that the effect is HSL-independent. A transcriptome analysis to dissect the effects of the P. aeruginosa supernatants on gene expression in the early stages of C. albicans biofilm formation identified 238 genes that exhibited reproducible changes in expression in response to all four supernatants. In particular, there was a strong increase in the expression of genes related to drug or toxin efflux and a decrease in expression of genes associated with adhesion and biofilm formation. Furthermore, expression of YWP1, which encodes a protein known to inhibit biofilm formation, was significantly increased. Biofilm formation is a key aspect of C. albicans infections, therefore the capacity of P. aeruginosa to antagonize this has clear biomedical implications.