A comprehensive analysis of the effect of quorum-sensing molecule 3-oxo-C12-homoserine lactone on Candida auris and Candida albicans

Abstract

Candida auris occupies similar niches in various infections as Pseudomonas aeruginosa; however, the details of their interspecies communication remain largely unknown. To gain deeper insights into this relationship, phenotypic and transcriptomic analyses were conducted in the presence of the primary P. aeruginosa quorum-sensing molecule, N-(3-oxododecanoyl)-l-homoserine lactone (HSL), against C. auris, with the results compared to those of C. albicans. Our findings indicate that HSL-induced effects are not specific to C. albicans; additionally, several characteristics are present in C. auris but not in C. albicans following HSL exposure. Significant HSL-induced reduction was observed in growth and adhesion of C. auris cells in time -and concentration-dependent way (p < 0.01-0.001). Moreover, HSL reduced intracellular iron and zinc levels (p < 0.05-0.001); furthermore, it modulated C. auris metabolism toward beta-oxidation, which may be associated with the observed reduction in in vivo virulence at lower HSL concentrations compared with C. albicans. RNA-sequencing transcriptome analysis of C. auris revealed 67 and 306 upregulated genes, as well as 111 and 168 downregulated genes, in response to 100 and 200-μM HSL, respectively. We identified 45 overlapping upregulated and 25 overlapping downregulated genes between the two HSL concentrations. Similar to other Candida-derived C12 compounds (e.g., farnesol), HSL reduces several C. auris survival strategies, which may significantly influence the nature of P. aeruginosa–C. auris co-habitation. In conclusion, the obtained findings on C. auris do not provide clear evidence that HSL mediated effects have any favourable consequences in terms of P. aeruginosa-C. auris co-colonisation and/or co-infections.