title: Comparative phenotypic analysis of the major fungal pathogens Candida parapsilosis and Candida albicans.
abstract: Candida parapsilosis and Candida albicans are human fungal pathogens that belong to the CTG 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 C. parapsilosis strains carrying double allele deletions of 100 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, and of CAP1 in the oxidative stress response. Others are unique to one species. For example, Cph2 plays a role in the hypoxic response in C. parapsilosis but not in C. albicans. We found extensive divergence between the biofilm regulators of the two species. We identified seven 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. 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, and that Cph2 and Bcr1 are major biofilm regulators in C. parapsilosis.
authors.affiliation: School of Biomedical and Biomolecular Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Holland
authors.affiliation: School of Biomedical and Biomolecular Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Markus S
authors.initials: MS
authors.lastname: Schröder
authors.affiliation: School of Biomedical and Biomolecular Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Siobhán A
authors.initials: SA
authors.lastname: Turner
authors.affiliation: Departments of Medicine and Microbiology and Immunology, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Heather
authors.initials: H
authors.lastname: Taff
authors.affiliation: Departments of Medicine and Microbiology and Immunology, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Andes
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Grózer
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
authors.affiliation: School of Biosciences, University of Exeter, Exeter, Devon, United Kingdom.
authors.forename: Lauren
authors.initials: L
authors.lastname: Ames
authors.affiliation: School of Biosciences, University of Exeter, Exeter, Devon, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Haynes
authors.affiliation: School of Medicine and Medical Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Desmond G
authors.initials: DG
authors.lastname: Higgins
authors.affiliation: School of Biomedical and Biomolecular Science, Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Butler
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D015415:Biomarkers / Q000032:analysis*; D002175:Candida / Q000145:classification* / Q000235:genetics* / Q000254:growth & development; D002177:Candidiasis / Q000235:genetics* / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013045:Species Specificity
chemical_list: D015415:Biomarkers; D005656:Fungal Proteins; D012331:RNA, Fungal; D012333:RNA, Messenger