A Pseudomonas aeruginosa quorum‐sensing molecule influences Candida albicans morphology

Abstract

SummaryCandida albicans is an opportunistic pathogen that is commonly found as a member of the human microflora. The ability of C. albicans to alter its cellular morphology has been associated with its virulence; yeast cells are more prevalent in commensal interactions whereas filamentous cells appear important in opportunistic infections. C. albicans encounters a multitude of other microbial species in the host environment and it is likely that they impact the C. albicans transition between virulent and non-virulent states. Here, we report that C. albicans morphology is significantly affected by the presence of Pseudomonas aeruginosa , another opportunistic pathogen. In a screen using a C. albicans HWP1-lacZ strain to indicate regions of filamentous growth, we identified P. aeruginosa mutants incapable of inhibiting C. albicans filamentation. Through these studies, we found that 3-oxo-C12 homoserine lactone, a cell-cell signalling molecule produced by P. aeruginosa , was sufficient to inhibit C. albicans filamentation without affecting fungal growth rates. Both microscopic analysis and real-time reverse transcription polymerase chain reaction analysis of morphology-specific markers confirmed that filamentation was suppressed by 200 m m m m M 3-oxo-C12 homoserine lactone. Structurally related compounds with a 12-carbon chain length, e.g. C12-acyl homoserine lactone and dodecanol also affected C. albicans filamentation at similar concentrations. In contrast, other acylated homoserine lactones of different chain lengths did not affect fungal morphology. The activity of 3OC12HSL is compared with that of farnesol, a C. albicans -produced molecule also with a C12-backbone. The effects that bacteria have on the morphology of C. albicans represents one of the ways by which bacteria can influence the behaviour of fungal cells.

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

“…To this end, we made use of a reporter construct developed by Uhl and Johnson (2001) in which the promoter of HWP1 was fused to the gene for β-galactosidase from Streptococcus thermophilus. Hyphal induction of C. albicans CAI-4 transformed with this construct can be determined via measurement of the activity of β-galactosidase (Uhl and Johnson, 2001;Hogan et al, 2004). By adapting the β-galactosidase assay to automated use in microtitre plate formats, we were able to identify three novel classes of antimycotic compounds in a pilot screening.…”

“…Candida albicans CAI-4 HWP1-lacZ (Hogan et al, 2004) was used in this study. Integration of lacZ upstream of the HWP1-promotor was confirmed by sequencing products of an uneven PCR executed according to the method of Chen and Wu (1996).…”

Cross-feeding and interkingdom communication in dual-species biofilms of Streptococcus mutans and Candida albicans

“…Hyphae development in C. albicans can be inhibited by 3-oxo-C12-homoserine lactone from Pseudomonas aeruginosa (Hogan et al, 2004), the S. mutans pheromone CSP (competence-stimulating peptide) (Jarosz et al, 2009) or by the diffusible signal factor trans-2-decenoic acid (Vilchez et al, 2010). Conversely, the signalling molecule farnesol from C. albicans inhibits the swarming motility of P. aeruginosa (McAlester et al, 2008) and induces the Pseudomonas quinolone signal synthesis (Cugini et al, 2010).…”

Catheter-related bloodstream infections: catheter management according to pathogen

“…Recent studies show interactions between C. albicans and P. aeruginosa in which P. aeruginosa forms a dense biofilm on C. albicans filaments and kills the fungus, but neither binds to nor kills yeast forms of C. albicans [27]. Furthermore, a P. aeruginosa quorum-sensing molecule (N-(3-oxododecanoyl) M a n u s c r i p t homoserine lactone) and structurally related compounds have been shown to be capable of suppressing filamentation in C. albicans cells [28].…”