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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.
Stefanini, Irene; Stoakes, Emily; Wu, Houdini H T; Xu-McCrae, Li; Hussain, Abid; Moat, John; Dowson, Christopher G; David, Miruna D; Constantinidou, Chrystala.
Afiliação
  • Stefanini I; Department of Life Sciences and Systems Biology, University of Turingrid.7605.4, Turin, Italy.
  • Stoakes E; Warwick Medical School, University of Warwickgrid.7372.1, Coventry, United Kingdom.
  • Wu HHT; UK Health Security Agency Public Health Laboratory, Birmingham, United Kingdom.
  • Xu-McCrae L; UK Health Security Agency Public Health Laboratory, Birmingham, United Kingdom.
  • Hussain A; UK Health Security Agency Public Health Laboratory, Birmingham, United Kingdom.
  • Moat J; School of Life Sciences, University of Warwick, Coventry, United Kingdom.
  • Dowson CG; School of Life Sciences, University of Warwick, Coventry, United Kingdom.
  • David MD; University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
  • Constantinidou C; Warwick Medical School, University of Warwickgrid.7372.1, Coventry, United Kingdom.
Microbiol Spectr ; 10(6): e0182722, 2022 12 21.
Article em En | MEDLINE | ID: mdl-36354359
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Candida glabrata / Antifúngicos Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Revista: Microbiol Spectr Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Candida glabrata / Antifúngicos Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Revista: Microbiol Spectr Ano de publicação: 2022 Tipo de documento: Article