Population genomics of the emerging yeast pathogen Candida glabrata
Year: 2018
Type: dissertation
Abstract: Infections caused by pathogenic fungi are becoming an increasingly serious threat for human health. Pathogenic fungi such as Candida glabrata or Candida albicans, belong to phylogenetically distinct clades and have non-pathogenic close relatives, indicating that the ability to infect humans has evolved several times independently. Despite the many recent advances in biomedicine, we are still lacking an understanding of how virulence evolves across organisms and which mechanisms are involved in the emergence of pathogenesis. Elucidating how human pathogens evolve is of central relevance to understand the bases of virulence and spread of infectious agents. In this context, population genomics provides a powerful tool to uncover recent selection pressures that can shed light on how pathogens adapt to humans. We here evaluated genomic and phenotypic variation across 57 C. glabrata strains. Firstly, we focused on 33 globally-distributed isolates. We catalogued extensive copy number variation, which we found to particularly affect genes encoding cell-wall associated proteins, including adhesins. This variation is structured into seven deeply divergent clades, which show recent geographical dispersion and large within-clade genomic and phenotypic differences. We show compelling evidence of recent admixture between differentiated lineages, and of purifying selection on mating genes, which provide first evidence for the existence of an active sexual (or parasexual) cycle in this yeast. Altogether, our results point to a recent global spread of previously genetically isolated populations and suggest that humans are only a secondary niche for this yeast. Secondly, we analyzed the genomic variability of C. glabrata in pairs of serial isolates, each from the same patient. We detected that patients can host clonal and non-clonal isolates. We observed an active standing genetic diversity with recurrent recombination leading to significant differences in terms of oxidative stress resistance biofilm formation. These results suggested that standing genetic variation and withinhost recombination between divergent strains may play an important role in disease progression and treatment outcome.
Authors: Carreté Muñoz, Laia
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2940305353