Azole heteroresistance in Cryptococcus neoformans: emergence of resistant clones with chromosomal disomy in the mouse brain during fluconazole treatment

E Sionov, YC Chang… - Antimicrobial agents and …, 2013 - Am Soc Microbiol
Antimicrobial agents and chemotherapy, 2013Am Soc Microbiol
We have previously reported that Cryptococcus neoformans strains are innately
heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due
to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the
emergence of heteroresistant clones in the brain during fluconazole treatment and found
that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain
dependent. Interestingly, emergence of heteroresistant clones in vivo was unrelated to the …
Abstract
We have previously reported that Cryptococcus neoformans strains are innately heteroresistant to fluconazole in vitro, producing minor, highly resistant subpopulations due to adaptive formation of disomic chromosomes. Using a mouse model, we assessed the emergence of heteroresistant clones in the brain during fluconazole treatment and found that the occurrence of heteroresistant clones in vivo with chromosomal disomy is strain dependent. Interestingly, emergence of heteroresistant clones in vivo was unrelated to the strain's MIC to fluconazole.
American Society for Microbiology