Study Title:

Candida Glabrata Infections on the Rise

Study Abstract

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.

From press release:

During the recent years yeasts have been causing more and more infections in humans. One of them can mutate surprisingly quickly by reorganizing its chromosomes. This enables this yeast to tolerate higher doses of anti-fungal medicine. This is shown by new research findings from the Lund University in Sweden.

A yeast named Candida glabrata commonly occurs in humans, usually on our skin. It does little harm there. But if it enters the blood system, it can be directly life threatening to people with poor immune defense, such as cancer and AIDS patients.

“It can actually eat you up from the inside,” says Jure Piškur, professor at the Department of Cell and Organism Biology at the Lund University.

Jure Piškur, together with a team of research colleagues, has studied the underlying reasons that this yeast can cause more and more infections in humans. The research team has discovered that Candida glabrata can mutate surprisingly rapidly. Instead of mutations occurring in individual genes, this yeast can mutate by reorganizing their chromosomes and make extra copies of large chromosome pieces.

The consequence of this is that Candida glabrata is becoming more and more resistant to fungicidal medicine. The present research report shows that a certain mini-chromosome can enable the yeast fungus to survive even if it is treated with nearly ten times the normal dose of the fungicide fluconazole.

”Our research now aims to identify the weak points in Candida glabrata so that we can develop effective medicine,” says Jure Piškur.

Candida glabrata has become the second most common yeast pathogen in humans. It primarily causes irritation, in the genitals, for instance. Jure Piškur stresses that people whose immune defense is normal run very little risk of being affected by the life-threatening form of fungal infection in the blood system.

The most common type of fungus in humans is called Candida albicans and causes commonly occurring infections in women’s genitals. This yeast fungus is relatively easy to treat with fungicides. But more and more often after the treatment Candida albicans is replaced with the more resistant Candida glabrata.

Study Information

Silvia Poláková, Christian Blume, Julián Álvarez Zárate, Marek Mentela, Dorte Jørck-Ramberg, Jørgen Stenderup and Jure Piškura.
Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata
Vetenskapsrådet (The Swedish Research Council) .
2009 February
Lund University in Sweden.

Full Study

http://www.pnas.org/content/106/8/2688.full.pdf+html