Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro
Year: 2020
Type: article
Abstract: Significance The incidence of infections due to fungal pathogens has dramatically increased in human populations with weakened or suppressed immune systems. Understanding how organisms rapidly adapt during human infection to enhance virulence and evolve drug resistance is important for developing effective treatments. We find that transposon mobilization in the human pathogen Cryptococcus causes genomic mutations in a murine model of infection and promotes resistance to antifungal drugs in vitro. Thermotolerance is a key virulence determinant for pathogenic fungi during the environment-to-host transition, and we demonstrate that a temperature increase is sufficient to trigger transposon mobilization in vitro. The link between temperature stress and transposon-associated mutations may significantly impact adaptation to the host during infection, including the acquisition of drug resistance.
Institution: Duke Medical Center
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Genetics of Cryptococcus sexual reproduction, G1072885028, G1394274318, Regulation of mitotic genome stability in yeast., G316281995, G3303573839, G5039032856, Coordinated Regulation of Virulence Genes in C. neoformans, Temperature-dependent transposon mobilization in Cryptococcus neoformans, G7212363089, G7391070412, G8021174655, Structure, function, and evolution of the Cryptococcus MAT locus, G9000046215, G9000118478, Impact of RNAi and unisexual reproduction on Cryptococcus evolution, drug resistance, and pathogenesis, Tri-Institutional Molecular Mycology and Pathogenesis Training Program
OpenAlex ID: W3017284745