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Genome dynamics and virulence in the human pathogen Candida glabrata

Ahmad, Khadija Mohamed LU (2014)
Abstract (Swedish)
Popular Abstract in English

Candida glabrata is currently the second most usual cause of yeast infections. This yeast is phylogenetically more related to Saccharomyces cerevisiae than to Candida albicans. Many systemic infections have recently been found associated with C. glabrata yeast. Apparently, this yeast can easily reshuffle its genome and this is one of the topics of my thesis.

During the last decades a few studies have been conducted to find out the mechanisms behind the pathogenicity of C. glabrata. Some of these studies have found that C. glabrata can adapt to the harsh conditions by changing the number and the size of chromosomes also intra- and inter-chromosomal segmental duplications have been... (More)
Popular Abstract in English

Candida glabrata is currently the second most usual cause of yeast infections. This yeast is phylogenetically more related to Saccharomyces cerevisiae than to Candida albicans. Many systemic infections have recently been found associated with C. glabrata yeast. Apparently, this yeast can easily reshuffle its genome and this is one of the topics of my thesis.

During the last decades a few studies have been conducted to find out the mechanisms behind the pathogenicity of C. glabrata. Some of these studies have found that C. glabrata can adapt to the harsh conditions by changing the number and the size of chromosomes also intra- and inter-chromosomal segmental duplications have been observed. One part of my study was to focus on the mechanisms involved in the genome rearrangements that are likely a way how to survive in the human and to become resistant to azole antifungal therapy. C. glabrata is an asexual yeast and only haploid isolates have been found so far.

Organisms can adapt to a new environment by rearranging their chromosomes. The ploidy and genomic instability have been reported to be associated with increased virulence.

In my thesis we generated hybrids of C. glabrata isolates and we let them grow under different stressful conditions including high temperature and the presence of azole. The aim of this experiment was to find out which strain, haploid or diploid, was more resistant to harsh environments. The competition was conducted in vitro and in vivo using the fly and mouse models. The genes that were highly expressed to overcome the

stress were elucidated by microarrays. Like other budding yeasts, C. glabrata has lost RNA interference pathway which is involved in the regulation of gene expression. In human, this pathway has been reported to play a crucial role in silencing genes related to some diseases. The scientists were able to silence some genes in Saccharomyces cerevisiae by reconstitution of RNAi system from Saccharomyces castellii. The beauty of this tool is that one can study the function of essential genes which can otherwise not be deleted. RNAi tool was successfully designed in our laboratory and we could silence URA3 and ADE2 and putative virulence genes and could study the resulting strains in the macrophage cell cultures. (Less)
Abstract
Although the yeast Candida glabrata is considered to be a part of the commensal microflora in healthy individuals, during the last years it has been frequently isolated from patients with mucosal and systemic fungal infections. Now it is considered as the second most frequently isolated pathogenic yeast after Candida albicans. Despite its name, C. glabrata is phylogenetically a closer relative to Saccharomyces cerevisiae than to

C. albicans. Apparently, C. glabrata has only recently changed its life style and become a successful opportunistic pathogen. It has been found that this yeast can rearrange its genome to cope the surrounding environments, and I show hereby that clinical isolates of C. glabrata show enormous genomic... (More)
Although the yeast Candida glabrata is considered to be a part of the commensal microflora in healthy individuals, during the last years it has been frequently isolated from patients with mucosal and systemic fungal infections. Now it is considered as the second most frequently isolated pathogenic yeast after Candida albicans. Despite its name, C. glabrata is phylogenetically a closer relative to Saccharomyces cerevisiae than to

C. albicans. Apparently, C. glabrata has only recently changed its life style and become a successful opportunistic pathogen. It has been found that this yeast can rearrange its genome to cope the surrounding environments, and I show hereby that clinical isolates of C. glabrata show enormous genomic plasticity. How this yeast reshuffles its genome to become a successful human pathogen remains to be elucidated.

During the last decades, several studies have been conducted to find out the mechanisms behind the pathogenicity of C. glabrata. Some studies have shown that C. glabrata can adapt to the harsh conditions by changing the number and size of chromosomes but intra- and inter-chromosomal segmental duplications have also been observed. Moreover, C. glabrata has become of great interest for researchers due to its

rapid development of antifungal drug resistance. Therefore, the mechanisms involved in genome rearrangement of C. glabrata to survive as a human pathogen and how it tolerates azole antifungal therapy is an interesting aspect to study. In this study I also developed a new tool, RNAi, to study putative virulence genes. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Castano, Irene, Department of Molecular Biology, Potosi Institute of Scientific Research & Technology, San Luis, Mexico.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Pathogenic yeast, Candida glabrata, small chromosomes, Genome rearrangement, Haploid and diploid yeast, RNA interference.
pages
200 pages
publisher
Department of Biology, Lund University
defense location
Biology House Lecture Hall, Sölvegatan 35, Lund.
defense date
2014-03-24 09:15
ISBN
978-91-7473-865-0
language
English
LU publication?
yes
id
5200378c-a1e8-4e59-9157-13f03548b81e (old id 4331909)
date added to LUP
2014-02-28 10:47:26
date last changed
2016-09-19 08:45:12
@misc{5200378c-a1e8-4e59-9157-13f03548b81e,
  abstract     = {Although the yeast Candida glabrata is considered to be a part of the commensal microflora in healthy individuals, during the last years it has been frequently isolated from patients with mucosal and systemic fungal infections. Now it is considered as the second most frequently isolated pathogenic yeast after Candida albicans. Despite its name, C. glabrata is phylogenetically a closer relative to Saccharomyces cerevisiae than to<br/><br>
C. albicans. Apparently, C. glabrata has only recently changed its life style and become a successful opportunistic pathogen. It has been found that this yeast can rearrange its genome to cope the surrounding environments, and I show hereby that clinical isolates of C. glabrata show enormous genomic plasticity. How this yeast reshuffles its genome to become a successful human pathogen remains to be elucidated.<br/><br>
During the last decades, several studies have been conducted to find out the mechanisms behind the pathogenicity of C. glabrata. Some studies have shown that C. glabrata can adapt to the harsh conditions by changing the number and size of chromosomes but intra- and inter-chromosomal segmental duplications have also been observed. Moreover, C. glabrata has become of great interest for researchers due to its<br/><br>
rapid development of antifungal drug resistance. Therefore, the mechanisms involved in genome rearrangement of C. glabrata to survive as a human pathogen and how it tolerates azole antifungal therapy is an interesting aspect to study. In this study I also developed a new tool, RNAi, to study putative virulence genes.},
  author       = {Ahmad, Khadija Mohamed},
  isbn         = {978-91-7473-865-0},
  keyword      = {Pathogenic yeast,Candida glabrata,small chromosomes,Genome rearrangement,Haploid and diploid yeast,RNA interference.},
  language     = {eng},
  pages        = {200},
  publisher    = {ARRAY(0xb0c5648)},
  title        = {Genome dynamics and virulence in the human pathogen Candida glabrata},
  year         = {2014},
}