Rapid Phenotypic and Genotypic Diversification After Exposure to the Oral Host Niche in Candida albicans

Genetics: A Periodical Record of Investigations Bearing on Heredity and Variation

Anja Forche^1¹  Tippapha Pisithkul^1²  Aleeza C. Gerstein^3³  Norma V. Solis^4⁴  Gareth Cromie^2⁵  Waracharee Srifa^1⁶ 

[1] Department of Biology, Bowdoin College, Brunswick, Maine 04011^1;Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095^4;Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota 55455^3;Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles Medical Center, Torrance, California 90502;Pacific Northwest Research Institute, Seattle, Washington 98122^2;School of Molecular Cell Biology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Israel^5

关键词: Candida albicans;    aneuploidy;    loss of heterozygosity;    oropharyngeal candidiasis;    hyper-variability;    colony phenotype;   

DOI  :  10.1534/genetics.118.301019

学科分类：医学（综合）

来源: Genetics Society of America

【 摘 要 】

In vitro studies suggest that stress may generate random standing variation and that different cellular and ploidy states may evolve more rapidly under stress. Yet this idea has not been tested with pathogenic fungi growing within their host niche in vivo . Here, we analyzed the generation of both genotypic and phenotypic diversity during exposure of Candida albicans to the mouse oral cavity. Ploidy, aneuploidy, loss of heterozygosity (LOH), and recombination were determined using flow cytometry and double digest restriction site-associated DNA sequencing. Colony phenotypic changes in size and filamentous growth were evident without selection and were enriched among colonies selected for LOH of the GAL1 marker. Aneuploidy and LOH occurred on all chromosomes (Chrs), with aneuploidy more frequent for smaller Chrs and whole Chr LOH more frequent for larger Chrs. Large genome shifts in ploidy to haploidy often maintained one or more heterozygous disomic Chrs, consistent with random Chr missegregation events. Most isolates displayed several different types of genomic changes, suggesting that the oral environment rapidly generates diversity de novo . In sharp contrast, following in vitro propagation, isolates were not enriched for multiple LOH events, except in those that underwent haploidization and/or had high levels of Chr loss. The frequency of events was overall 100 times higher for C. albicans populations following in vivo passage compared with in vitro . These hyper-diverse in vivo isolates likely provide C. albicans with the ability to adapt rapidly to the diversity of stress environments it encounters inside the host.

【 授权许可】

CC BY