Transcriptional Responses of Candida albicans to Epithelial and Endothelial Cells

Abstract

Candida albicans interacts with oral epithelial cells during oropharyngeal candidiasis and with vascular endothelial cells when it disseminates hematogenously. We set out to identify C. albicans genes that govern interactions with these host cells in vitro. The transcriptional response of C. albicans to the FaDu oral epithelial cell line and primary endothelial cells was determined by microarray analysis. Contact with epithelial cells caused a decrease in transcript levels of genes related to protein synthesis and adhesion, whereas contact with endothelial cells did not significantly influence any specific functional category of genes. Many genes whose transcripts were increased in response to either host cell had not been previously characterized. We constructed mutants with homozygous insertions in 22 of these uncharacterized genes to investigate their function during host-pathogen interaction. By this approach, we found that YCK2, VPS51, and UEC1 are required for C. albicans to cause normal damage to epithelial cells and resist antimicrobial peptides. YCK2 is also necessary for maintenance of cell polarity. VPS51 is necessary for normal vacuole formation, resistance to multiple stressors, and induction of maximal endothelial cell damage. UEC1 encodes a unique protein that is required for resistance to cell membrane stress. Therefore, some C. albicans genes whose transcripts are increased upon contact with epithelial or endothelial cells are required for the organism to damage these cells and withstand the stresses that it likely encounters during growth in the oropharynx and bloodstream.

New signaling pathways govern the host response to C. albicans infection in various niches

“…The list of genes that were found to be differentially expressed does not overlap significantly with either of these previous studies. For example, of the 127 genes that were differentially expressed during at least one time point in one cell type in the current study, five were reported by Park et al (2009) and 11 were reported by Wachtler et al (2011) to have changed in the same direction. There are several possible explanations for the poor concordance.…”

“…Cold Spring Harbor Laboratory Press on April 27, 2019 -Published by genome.cshlp.org Downloaded from To our knowledge, only two other studies, both microarraybased, examined the response of epithelial cells or endothelial cells to C. albicans using a similar time-matched negative control sample that consisted of fungal cells incubated in tissue culture media without host cells (Park et al 2009;Wachtler et al 2011). The list of genes that were found to be differentially expressed does not overlap significantly with either of these previous studies.…”

“…Therefore, the most likely explanation for the discordance with this study is the difference in host cells and the timing of the experiment. For the Park study, the analysis was done on FaDu oral epithelial cells at 45, 90, and 180 min post-infection with clinical isolates that differ from the C. albicans strain, SC5314 (Park et al 2009). So, the most likely explanation for the discordance with this study is the combination of different host cells as well as the different C. albicans strains examined.…”

“…Previous studies have used microarrays to individually examine the transcriptional response of C. albicans to endothelial or epithelial cells (Müller et al 2007;Barker et al 2008;Lim et al 2011;Ikuta et al 2012;Moyes et al 2014), as well as the transcriptional response of these host cells to infection by C. albicans (Sandovsky-Losica et al 2006;Zakikhany et al 2007;Park et al 2009;Martin et al 2011;Wachtler et al 2011). Although these studies have contributed to our understanding of the interaction between pathogen and host, the full catalog of transcriptional changes is not complete owing to the limitations of microarrays, which include limited dynamic range and poor sensitivity to analyze low abundance transcripts.…”

Site-Directed and Random Insertional Mutagenesis in Medically Important Fungi

“…This allowed for the construction of a large set of mutants, though it was still not as efficient as it would be for a haploid strain. This library is widely used by the Candida community Norice et al, 2007;Park et al, 2009). Spreghini et al (2003) exploited transposon mutagenesis to add an epitope to the putative cell wall protein, Dfg5p.…”