Data supporting "Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in vitro and in vivo"

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https://doi.org/10.13020/pg0z-ag23
https://hdl.handle.net/11299/259321

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Keywords

Candida albicans

fluorescent reporter

copy number change

fitness

Collection period

2022-01-04
2023-03-29

Date completed

2025-01-01

Date updated

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Title

Data supporting "Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in vitro and in vivo"

Published Date

2024-01-04

Authors

Zhou, Xin

Hilk, Audrey

Solis, Norma V

Scott, Nancy

Beach, Annette

Soisangwan, Natthapon

Billings, Clara L

Burrack, Laura S

Filler, Scott G

Selmecki, Anna

Group

University of Minnesota Selmecki lab

Author Contact

Anna Selmecki
Selmecki@umn.edu

Type

Dataset

Abstract

Genomic copy number changes are associated with antifungal drug resistance and virulence across diverse fungal pathogens. Despite the high prevalence of both gain and loss events, the rate and dynamics of these genomic changes in the presence of antifungal drugs is not known for any organism. We optimized a dual-fluorescent reporter system in the diploid pathogen Candida albicans to quantify copy number variation (CNV) and loss of heterozygosity (LOH) at the single cell level with flow cytometry. We followed the rate and dynamics of CNV and LOH at two distinct genomic locations during parallel evolution experiments in the presence and absence of antifungal drugs in vitro and in a murine model of infection. Copy number changes were rapid and dynamic during adaptation to three different concentrations of the azole drug fluconazole. The fluorescent reporters revealed competing sub-populations with distinct genotypes in the drug-evolved lineages. Extensive whole genome sequencing identified recurrent genotypes that cause increased competitive fitness in the presence of antifungal drug. Specifically, at low concentrations of drug, chromosome 3 (Chr3) LOH frequently arose and led to significantly increased competitive fitness. In contrast, at high drug concentrations, Chr3 and Chr6 aneuploidy arose together, and these concurrent aneuploidies conferred multi-azole tolerance. In the murine model, copy number changes were only detected in isolates recovered from mice treated with fluconazole, and included whole-genome duplication events resulting in polyploidy. This study provides the first quantitative evidence for the incredible speed at which diverse genotypes arise and undergo dynamic population-level fluctuations during adaptation to antifungal drugs in vitro and in vivo.  

Description

Most of data are flow cytometry data with file format .fcs and supplemented with a readme file (.pdf) providing the sample name and layout. There are also some yeast growth curve data with file format .xlsx

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License

CC0 1.0 Universal
http://creativecommons.org/publicdomain/zero/1.0/

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Data Repository for U of M (DRUM)

Funding information

National Institutes of Health (R01 AI143689)
Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases Award (#1020388)

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Suggested citation

Zhou, Xin; Hilk, Audrey; Solis, Norma V; Scott, Nancy; Beach, Annette; Soisangwan, Natthapon; Billings, Clara L; Burrack, Laura S; Filler, Scott G; Selmecki, Anna. (2024). Data supporting "Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in vitro and in vivo". Retrieved from the University Digital Conservancy, https://doi.org/10.13020/pg0z-ag23.

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