ABSTRACT
We analyzed 192 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985-1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained small chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes, and some of these resulting "mutant" strains can have increased fitness in a certain patient "environment".
Subject(s)
Candida glabrata/ultrastructure , Chromosomes, Fungal/ultrastructure , Antifungal Agents/pharmacology , Base Sequence , Candida glabrata/drug effects , Candida glabrata/genetics , Candida glabrata/isolation & purification , Candidiasis/microbiology , Cross Infection/microbiology , DNA, Fungal/genetics , DNA, Ribosomal , Denmark , Drug Resistance, Fungal/genetics , Evolution, Molecular , Fluconazole/pharmacology , Fungemia/microbiology , Gene Duplication , Genes, Fungal , Genomic Instability , Haploidy , Humans , Karyotyping , Molecular Sequence Data , Phylogeny , Selection, Genetic , Species Specificity , Translocation, GeneticABSTRACT
In eukaryotes, the number and rough organization of chromosomes is well preserved within isolates of the same species. Novel chromosomes and loss of chromosomes are infrequent and usually associated with pathological events. Here, we analyzed 40 pathogenic isolates of a haploid and asexual yeast, Candida glabrata, for their genome structure and stability. This organism has recently become the second most prevalent yeast pathogen in humans. Although the gene sequences were well conserved among different strains, their chromosome structures differed drastically. The most frequent events reshaping chromosomes were translocations of chromosomal arms. However, also larger segmental duplications were frequent and occasionally we observed novel chromosomes. Apparently, this yeast can generate a new chromosome by duplication of chromosome segments carrying a centromere and subsequently adding novel telomeric ends. We show that the observed genome plasticity is connected with antifungal drug resistance and it is likely an advantage in the human body, where environmental conditions fluctuate a lot.
Subject(s)
Candida glabrata/genetics , Chromosomes, Fungal , Virulence/genetics , Antifungal Agents/pharmacology , Base Sequence , Blotting, Southern , Candida glabrata/drug effects , Candida glabrata/pathogenicity , DNA Primers , Electrophoresis, Gel, Pulsed-Field , Phylogeny , Polymerase Chain ReactionABSTRACT
Many pathogenic yeast species are asexual and therefore not involved in intra- or interspecies mating. However, high-frequency transfer of plasmid DNA was observed when pathogenic and food-borne yeasts were grown together. This property could play a crucial role in the spread of virulence and drug resistance factors among yeasts.
