Understand the genomic diversity and evolution of fungal pathogen Candida glabrata by genome-wide analysis of genetic variations
Artikel i vetenskaplig tidskrift, 2019

The yeast Candida glabrata, an opportunistic human fungal pathogen, is the second most prevalent cause of candidiasis worldwide, with an infection incidence that has been increasing in the past decades. The completion of the C. glabrata reference genome made fundamental contributions to the understanding of the molecular basis of its pathogenic phenotypes. However, knowledge of genome-wide genetic variations among C. glabrata strains is limited. In this study, we present a population genomic study of C. glabrata based on whole genome re-sequencing of 47 clinical strains to an average coverage of ∼63×. Abundant genetic variations were identified in these strains, including single nucleotide polymorphisms (SNPs), small insertion/deletions (indels) and copy number variations (CNVs). The observed patterns of variations revealed clear population structure of these strains. Using population genetic tests, we detected fast evolution of several genes involved in C. glabrata adherence ability, such as EPA9 and EPA10. We also located genome structural variations, including aneuploidies and large fragment CNVs, in regions that are functionally related to virulence. Subtelometric regions were hotspots of CNVs, which may contribute to variation in expression of adhesin genes that are important for virulence. We further conducted a genome-wide association study that identified two SNPs in the 5′UTR region of CST6 that were associated with fluconazole susceptibility. These observations provide convincing evidence for the highly dynamic nature of the C. glabrata genome with potential adaptive evolution to clinical environments, and offer valuable resources for investigating the mechanisms underlying drug resistance and virulence in this fungal pathogen. (249 words)

Evolution of virulence

Candida glabrata

Population genomics

Genome dynamics

Författare

Xiaoxian Guo

Cornell University

Ruoyu Zhang

Cornell University

Yudong Li

Zhejiang Gongshang University

Cornell University

Zhe Wang

Cornell University

Olena Ishchuk

Lunds universitet

Chalmers, Biologi och bioteknik, Systembiologi

Khadija M. Ahmad

Lunds universitet

Josephine Wee

Cornell University

Jure Piškur

Lunds universitet

Joshua A. Shapiro

Bryn Mawr College

Zhenglong Gu

Cornell University

Methods

1046-2023 (ISSN) 1095-9130 (eISSN)

Vol. In Press

Ämneskategorier

Medicinsk bioteknik

DOI

10.1016/j.ymeth.2019.05.002

Mer information

Senast uppdaterat

2019-12-02