Transposon mobilization in the human fungal pathogen <i>Cryptococcus</i> is mutagenic during infection and promotes drug resistance in vitro
Asiya Gusa, Jonathan Williams, Jang-Eun Cho, Anna Floyd Averette, Sheng Sun, Eva Mei Shouse, Joseph Heitman, J. Andrew Alspaugh, Sue Jinks-Robertson
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.