Some fungal pathogens survive antifungal drugs by mutating. But Aspergillus fumigatus, a common mold, has a stealthier strategy: it duplicates entire chromosomes, rides out the threat, then discards the extra genetic material once the pressure lifts — leaving no trace that resistance ever occurred.
Duke University School of Medicine PhD candidate Anna Lehmann made the discovery while working in the lab of Joseph Heitman, MD, PhD, James B. Duke Distinguished Professor and chair of the Department of Molecular Genetics and Microbiology. Her findings, published in the July 2026 issue of Current Biology, establish the first evidence that A. fumigatus can gain and lose entire chromosomes.
Aspergillus fumigatus is found in in soil, compost, and decaying vegetation and has been designated a critical priority fungal pathogen by the World Health Organization. Most people inhale its spores daily without consequence, but for immunocompromised individuals, it can cause invasive aspergillosis, a life-threatening infection with high mortality.
"This discovery reveals a remarkable level of genetic flexibility in this pathogen," Heitman said. "It fundamentally changes our understanding of how Aspergillus fumigatus can adapt to stressful environments, including exposure to antifungal drugs."
Lehmann’s path to the finding reflects the same persistence she brings to competitive cross-country skiing. “Both require consistent dedication over months and years, and progress is often incremental,” said Lehmann. She first became interested in A. fumigatus as an undergraduate in the lab of Robert A. Cramer, PhD, at Dartmouth, where mentors encouraged her to pursue independent ideas.
In the Heitman lab, Lehmann began exposing Aspergillus to FK506, a compound that inhibits a critical cellular signaling pathway. Some fungal colonies unexpectedly regained the ability to grow. Determining why required computational skills Lehmann didn't yet have — so she learned them, and sought out collaborators.
Genetic analysis revealed the answer: the surviving fungi had duplicated entire chromosomes. Critically, the duplications proved unstable. Once drug pressure was removed, the fungi rapidly shed the extra chromosomes and returned to their original genetic state, which may explain why this form of resistance has remained hidden.
Beyond a Single Drug
Lehmann also found that the chromosome duplications conferred resistance beyond FK506. Several strains showed reduced susceptibility to azoles, a frontline class of antifungal drugs — a finding that deepens concern about resistance at a time when treatment options are already limited.
"Compared with bacterial infections, we have relatively few antifungal drugs available," said Andrew Alspaugh, MD, professor of medicine in Duke's Division of Infectious Diseases and a member of Lehmann's dissertation committee. "When resistance emerges, there are often fewer alternatives for patients."
The findings also raise questions about resistance developing outside the clinic. Azoles are widely used in agriculture to protect crops, and prior research has linked agricultural use to resistant strains capable of infecting humans. Heitman said Lehmann's work suggests transient resistance may be emerging in nature and escaping detection because it disappears once selective pressure is removed.
The Duke team is now exploring whether similar chromosome duplications occur in environmental and clinical samples of A. fumigatus — findings that could prompt a rethinking of how antifungal resistance is detected and monitored.
Lehmann hopes to one day lead her own research group focused on fungal pathogenesis and treatment failure.
"In our lab, there are talented and accomplished people at every level," Lehmann said. "Having successful people to look up to motivates me to reach for the next level."