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Transcription Profiles Associated with Inducible Adhesion in Candida parapsilosis

ABSTRACT: 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 function that may have an important role in this important step for colonization and disease.

ORGANISM(S): Candida parapsilosis

PROVIDER: GSE159274 | GEO | 2021/02/01

REPOSITORIES: GEO

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Project description:Abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CUG clade in the Saccharomycotina. In contrast to C. albicans, relatively little is known about the virulence properties of C. parapsilosis, a pathogen particularly associated with infections of premature neonates. We describe here the construction of >200 C. parapsilosis strains carrying double allele deletions of transcription factors, protein kinases and species-specific genes. Two independent deletions were constructed for each target gene. Growth in > 40 conditions was tested, including carbon source, temperature, and the presence of antifungal drugs. The phenotypes were compared to C. albicans strains with deletions of orthologous transcription factors. We found that many phenotypes are shared between the two species, such as the role of Upc2 as a regulator of azole resistance. Others are unique. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis and not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified 7 transcription factors and one protein kinase that are required for biofilm development in C. parapsilosis. Only three (Efg1, Bcr1, and Ace2) have similar effects on C. albicans biofilms, whereas Cph2, Czf1, Gzf3 and Ume6 have major roles in C. parapsilosis only. In addition, two transcription factors (Brg1 and Tec1) with well-characterized roles in biofilm formation in C. albicans do not have the same function in C. parapsilosis. We also compared the transcription profile of C. parapsilosis and C. albicans biofilms. Our analysis suggests the processes shared between the two species are predominantly metabolic. C. parapsilosis mRNA profiles of wild type (WT) at 37 degree celcius in planktonic growth conditions and ace2-/-, cph2-/-, efg1-/-, czf1-/-, ume6-/-, bcr1-/- and WT in biofilm conditions were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.

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Transcription Profiles Associated with Inducible Adhesion in Candida parapsilosis

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