Transcription Profiles Associated with Inducible Adhesion in Candida parapsilosis

Candida parapsilosis has emerged as a frequent cause of invasive candidiasis with increasing evidence of unique biological features relative to C. albicans As it adapts to conditions within a mammalian host, rapid changes in gene expression are necessary to facilitate colonization and persistence in this environment. Adhesion of the organism to biological surfaces is a key first step in this process and is the focus of this study. Building on previous observations showing the importance of a member of the ALS gene family in C. parapsilosis adhesion, three clinical isolates were cultured under two conditions that mimic the mammalian host and promote adhesion, incubation at 37°C in tissue culture medium 199 or in human plasma. Transcriptional profiles using RNA-seq were obtained in these adhesion-inducing conditions and compared to profiles following growth in yeast media that suppress adhesion to identify gene expression profiles associated with adhesion. Overall gene expression profiles among the three strains were similar in both adhesion-inducing conditions and distinct from adhesion-suppressing conditions. Pairwise analysis among the three growth conditions identified 133 genes that were differentially expressed at a cutoff of ±4-fold, with the most upregulated genes significantly enriched in iron acquisition and transmembrane transport, while the most downregulated genes were enriched in oxidation-reduction processes. Gene family enrichment analysis identified gene families with diverse functions that may have an important role in this important step for colonization and disease.IMPORTANCE Invasive Candida infections are frequent complications of the immunocompromised and are associated with substantive morbidity and mortality. Although C. albicans is the best-studied species, emerging infections by non-albicans Candida species have led to increased efforts to understand aspects of their pathogenesis that are unique from C. albicansC. parapsilosis is a frequent cause of invasive infections, particularly among premature infants. Recent efforts have identified important virulence mechanisms that have features distinct from C. albicansC. parapsilosis can exist outside a host environment and therefore requires rapid modifications when it encounters a mammalian host to prevent its clearance. An important first step in the process is adhesion to host surfaces. This work takes a global, nonbiased approach to investigate broad changes in gene expression that accompany efficient adhesion. As such, biological pathways and individual protein targets are identified that may be amenable to manipulation to reduce colonization and disease from this organism.