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Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures

Author

Listed:
  • Hassan Badrane

    (University of Pittsburgh)

  • Shaoji Cheng

    (University of Pittsburgh)

  • Christopher L. Dupont

    (J. Craig Venter Institute)

  • Binghua Hao

    (University of Pittsburgh)

  • Eileen Driscoll

    (University of Pittsburgh)

  • Kristin Morder

    (University of Pittsburgh)

  • Guojun Liu

    (University of Pittsburgh)

  • Anthony Newbrough

    (University of Pittsburgh)

  • Giuseppe Fleres

    (University of Pittsburgh)

  • Drishti Kaul

    (J. Craig Venter Institute)

  • Josh L. Espinoza

    (J. Craig Venter Institute)

  • Cornelius J. Clancy

    (University of Pittsburgh
    VA Pittsburgh Healthcare System)

  • M. Hong Nguyen

    (University of Pittsburgh)

Abstract

The longstanding model is that most bloodstream infections (BSIs) are caused by a single organism. We perform whole genome sequencing of five-to-ten strains from blood culture (BC) bottles in each of ten patients with Candida glabrata BSI. We demonstrate that BCs contain mixed populations of clonal but genetically diverse strains. Genetically distinct strains from two patients exhibit phenotypes that are potentially important during BSIs, including differences in susceptibility to antifungal agents and phagocytosis. In both patients, the clinical microbiology lab recovered a fluconazole-susceptible index strain, but we identify mixed fluconazole-susceptible and –resistant populations. Diversity in drug susceptibility is likely clinically relevant, as fluconazole-resistant strains were subsequently recovered by the clinical laboratory during persistent or relapsing infections. In one patient, unrecognized respiration-deficient small colony variants are fluconazole-resistant and significantly attenuated for virulence during murine candidiasis. Our data suggest a population-based model of C. glabrata genotypic and phenotypic diversity during BSIs.

Suggested Citation

  • Hassan Badrane & Shaoji Cheng & Christopher L. Dupont & Binghua Hao & Eileen Driscoll & Kristin Morder & Guojun Liu & Anthony Newbrough & Giuseppe Fleres & Drishti Kaul & Josh L. Espinoza & Cornelius , 2023. "Genotypic diversity and unrecognized antifungal resistance among populations of Candida glabrata from positive blood cultures," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41509-x
    DOI: 10.1038/s41467-023-41509-x
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    References listed on IDEAS

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    1. Bernard Dujon & David Sherman & Gilles Fischer & Pascal Durrens & Serge Casaregola & Ingrid Lafontaine & Jacky de Montigny & Christian Marck & Cécile Neuvéglise & Emmanuel Talla & Nicolas Goffard & Li, 2004. "Genome evolution in yeasts," Nature, Nature, vol. 430(6995), pages 35-44, July.
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