Identifying infection-associated genes ofCandida albicansin the postgenomic era

Abstract

The human pathogenic yeast Candida albicans can cause an unusually broad range of infections reflecting a remarkable potential to adapt to various microniches within the human host. The exceptional adaptability of C. albicans is mediated by rapid alterations in gene expression in response to various environmental stimuli and this transcriptional flexibility can be monitored with tools such as microarrays. Using such technology it is possible to (1) capture a genome-wide portrait of the transcriptome that mirrors the environmental conditions, (2) identify known genes, signalling pathways and transcription factors involved in pathogenesis, (3) identify new patterns of gene expression and (4) identify previously uncharacterized genes that may be associated with infection. In this review, we describe the molecular dissection of three distinct stages of infections, covering both superficial and invasive disease, using in vitro, ex vivo and in vivo infection models and microarrays.

Epithelial Cells and Innate Antifungal Defense

“…Although the model consists of transformed cells (cell line TR146 derived from a carcinoma of the oral epithelium) (Rupniak et al, 1985), all natural major markers of the epithelial basement membrane and of epithelial differentiation are expressed. More important, despite the artificiality of the model, it behaves like human in vivo epithelium when treated with pathogens and pharmacologically active agents, respectively (Schaller and Weindl, 2009), and it mimics the clinical setting of C. albicans infections in the oral cavity (Wilson et al, 2009). Analysis of the oral RHE by real-time RT-PCR demonstrated a high degree of similarity in TLR expression profiles between the oral RHE and buccal epithelial samples isolated from healthy individuals (Weindl et al, 2007).…”

Proteolytic Cleavage of Covalently Linked Cell Wall Proteins by Candida albicans Sap9 and Sap10

“…However, even a mildly compromised immune system or a minor imbalance of the microbiota can be sufficient for C. albicans to cause superficial skin or mucosal infections (50). Furthermore, in cases of impaired immunity or disruption of natural barriers, C. albicans can cause fatal systemic disease, disseminating throughout the bloodstream and infecting internal organs (53,60,73).…”

Budding off: bringing functional genomics toCandida albicans

“…Expression profiling has also been performed using C. albicans cells grown on either reconstituted human oral epithelia or epithelial monolayers [113,114]. Here, gene transcription reflected the various chronological stages of attachment, hyphal production, cell invasion and tissue destruction [99]. A similarly ordered transcriptional profile was also identified using a murine model of vulvovaginal candidiasis [115,116].…”

“…RNA-Seq studies have identified 600 novel coding and over 1000 noncoding transcripts in C. albicans, many of which are regulated by environment and cell state [97,98]. Transcriptional profiles have now been defined under a wide variety of conditions both in vitro and in vivo [99][100][101][102][103]. Profiling of unique phenotypic states, including white, opaque, gray and GUT (gastrointestinally induced transition), has been used to define the transcriptional networks regulating these states, and has revealed that these networks resemble those controlling cell fate in metazoans [34,75,98,104].…”