ABSTRACT
Candida albicans is a major opportunistic pathogen of humans. Previous work has demonstrated the existence of a general-purpose genotype (GPG; equivalent to clade 1 as defined by multi-locus sequence typing data) that is more frequent than other genotypes as an agent of human disease and commensal colonization. We undertook a genomic screen which indicated that a large number of mutations differentiate GPG strains from other strains and that such mutations are scattered throughout the genome. GPG-specific mutations are non-synonymous more frequently than expected by chance, and are not randomly distributed across functional and structural gene categories. Our analysis has identified three categories of genes in which GPG-specific mutations are over-represented, namely genes for which expression changes during the yeast-hyphal transition, genes for which expression changes as a result of exposure to antifungal agents and repeat-containing ORFs. Although we have no direct evidence that the individual polymorphisms identified confer selective advantages to GPG strains, the results support our contention that the high prevalence of GPG strains is not merely due to genetic drift but that GPG strains have reached a high prevalence because they possess a multitude of fitness-enhancing traits. They also indicate that the distribution of genes marked by GPG-specific mutations across functional and structural categories could identify physiological traits that are of particular importance to the success of GPG strains in their interactions with the human host.
Subject(s)
Candida albicans/genetics , Candida albicans/pathogenicity , Candidiasis/microbiology , Genome, Fungal , Polymorphism, Genetic , Amplified Fragment Length Polymorphism Analysis , DNA, Fungal , Data Interpretation, Statistical , Genes, Fungal , Genotype , Humans , Molecular Sequence Data , Mutation , Open Reading Frames , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNAABSTRACT
Three steroidal saponins, including one new and two known compounds, were isolated from the rhizomes of Paris polyphylla Smith. One- and two-dimensional NMR, LC-MS, and interpretation of hydrolytic cleavage experiments led to the identification of the structure of the new saponin as ( 25R)-spirost-5-ene-3 beta,17 alpha-diol (pennogenin) 3- O-{ O- alpha- L-rhamnopyranosyl-(1-->2)- O-[ O- beta-xylopyranosyl-(1-->5)- alpha- L-arabinofuranosyl-(1-->4)]- beta- D-glucopyranoside}. The isolated saponins were evaluated for their antifungal activity against Cladosporium cladosporioides and Candida species and showed comparable activity to chemicals used in some commercial products.
