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

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 J. Clancy and M. Hong Nguyen ()
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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
M. Hong Nguyen: University of Pittsburgh

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41509-x

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