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Genomic Assembly of Clinical Candida glabrata (Nakaseomyces glabrata) Isolates Reveals within-Species Structural Plasticity and Association with In Vitro Antifungal Susceptibility
10.1128/spectrum.01827-22
Irene Stefanini
Emily Stoakes
Houdini H. T. Wu
Li Xu-McCrae
Abid Hussain
John Moat
Christopher G. Dowson
Miruna D. David
Chrystala Constantinidou
Research Article
Research Article
Candida glabrata
antifungals
antimicrobial resistance
genomics
population genetics
American Society for Microbiology
Stefanini et al.
Copyright © 2022 Stefanini et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
20221110
2022
ABSTRACT
The opportunistic human pathogen Candida glabrata has become an increasingly important threat to human health, with infections globally characterized by high mortality rates and multidrug resistance. To face this threat, more efficient diagnostic and therapeutic approaches are required, underpinning research to help define the intraspecies epidemiology, genetic variability, and therefore, diagnostic and therapeutic target stability. Previous comparative genetics studies conducted on limited numbers of strains only revealed partial resolution of chromosomal settings. In this study, by combining short- and long-read genome sequencing, phenotypic characterization, and comparative genomics over a large set of strains, we detected strict relationships between large chromosomal rearrangements and phylogenetic clades, genes subjected to different selective pressures, and new sets of genes associated with resistance to antifungals. Overall, these results not only provide a fundamental contribution to our knowledge of C. glabrata evolution and epidemiology but may also lay the foundations for the future development of tailored therapeutic approaches.
IMPORTANCE The human pathogen Candida glabrata has become a global threat to human health, with infections characterized by high mortality and multidrug resistance. We have obtained nine fully assembled genomes from clinical isolates through a combination of short- and long-read sequencing approaches. The quality and completeness of such genomes and their subsequent comparison to the broadest set of genomes so far allowed us to pinpoint chromosomal rearrangements in several genomes and detect phylogenetic clades that were not associated with geographic location or isolation source. We identified a new set of genes associated with resistance to antifungals coding for adhesin or adhesin-like proteins, suggesting C. glabrata resists antifungals by forming aggregates or adhering to the host tissue. These results, which provide a fundamental contribution to our knowledge of C. glabrata evolution and epidemiology, may initiate the development of precision medicine interventions for patients with suspected or proven invasive fungal infections.
20220520
20221019
2165-0497
Adobe LiveCycle PDF Generator; modified using iText® 5.5.13.2 ©2000-2020 iText Group NV (AGPL-version)2023-01-04T06:37:51-08:00
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