Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans

Abstract

Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 species-specific genes are identified, including some encoding known hyphal-specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis are orthologs of several filamentous growth regulator (FGR) genes that also have suspected roles in pathogenesis. However, the principal differences in genomic repertoire concern expansion of the TLO gene family of putative transcription factors and the IFA family of putative transmembrane proteins in C. albicans, which represent novel candidate virulence-associated factors. The results suggest that the recent evolutionary histories of C. albicans and C. dubliniensis are quite different. While gene families instrumental in pathogenesis have been elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key pathogenic functions. This could explain why C. albicans is a more potent pathogen in humans than C. dubliniensis.

Discovery of the gray phenotype and white-gray-opaque tristable phenotypic transitions inCandida dubliniensis

“…It has been suggested that C. dubliniensis is more capable of developing antifungal resistance (e.g., to azoles) than C. albicans. 9,12,14 This feature of C. dubliniensis may be associated with its prevalence in AIDS patients, who are often subjected to antifungal treatments. Our results showing the upregulated expression of a number of ergosterol biosynthesis genes in gray cells of C. dubliniensis provide a potential explanation for this phenomenon.…”

“…3,11,12 Epidemiological studies indicate that C. dubliniensis is primarily associated with human immunodeficiency virus (HIV)-infected patients. [6][7][8][9] A number of comparative genomic and phenotypic studies of C. albicans and C. dubliniensis have been performed in the previous 2 decades, [12][13][14][15] but what underlying mechanisms or biological characteristics underlying the differences between the 2 species in epidemiology, virulence, and the ability to develop antifungal resistance remain to be investigated.…”

Functional Genomics of Candida albicans

“…Except for Lodderomyces elongisporus, the other five species are all pathogenic and often isolated from clinical sources. The genome sequence of Candida dubliniensis, a closely related species of C. albicans, has also been sequenced by Jackson et al [6]. Comparative analysis of the genome sequences of these pathogenic and non-pathogenic species not only identifies a lot of new genes, but also a number of species-specific virulence factors.…”

“…Comparative analysis of the genome sequences of these pathogenic and non-pathogenic species not only identifies a lot of new genes, but also a number of species-specific virulence factors. The pathogenic Candida species show significant expansion of several gene families including those encoding cell wall, secreted and transporter proteins [6]. For example, the Als adhesins, which are associated with virulence in C. albicans, are enriched in pathogenic species but not found in non-pathogenic species like Saccharomyces cerevisiae.…”

Novel Definition and Algorithm for Chaining Fragments with Proportional Overlaps

“…In biology, genome comparison is used for gene annotation, phylogenetic studies, and even vaccine design [12,2,8]. Many bioinformatics programs for whole genome comparison involve a fragment chaining step, which seeks to maximize the total length of the chained fragments (eg, [7]).…”