Transposons, Heat Stress, and Drug Resistance: How Cryptococcus Adapts Inside the Host
When we think about fungal pathogens, we often picture them as static invaders — organisms that infect, persist, and sometimes evade drugs through slow, incremental mutations. But new research reveals that some fungi possess a far more dynamic evolutionary toolkit.
A 2020 study by Asiya Gusa, Jonathan Williams, Sue Jinks-Robertson, and colleagues at Duke University published in Proceedings of the National Academy of Sciences (PNAS) has uncovered a striking mechanism by which the human fungal pathogen Cryptococcus adapts to hostile host environments: temperature-driven mobilization of transposable elements (TEs)gusa-et-al-2020-transposon-mobi….
What Are Transposable Elements?
Transposable elements (TEs), often called “jumping genes,” are DNA sequences capable of moving from one genomic location to another. They were first discovered by Barbara McClintock in the 1940s in maize and have since been found across all domains of life. In fungi, they make up a significant portion of the genome (∼14%), and their movement can create mutations, alter gene expression, and drive evolutionary change.
In Cryptococcus deneoformans, the study identified two major players:
T1 DNA transposon
TCN12 retrotransposon
Both of these were shown to actively insert into genes during infection, disrupting normal function and, in many cases, conferring drug resistance.
Heat Stress Triggers Genomic Chaos
One of the most remarkable findings of the Gusa et al. study was that host temperature (37°C) directly triggered TE mobilization.
At typical laboratory growth temperatures (30°C), transposon movement was rare. But when Cryptococcus was exposed to mammalian body temperature, TE insertion rates skyrocketed — in some cases 200-fold higher. This led to widespread mutations, many of which conferred resistance to antifungal drugs such as:
5-fluoroorotic acid (5FOA) via mutations in URA3 or URA5
Rapamycin/FK506 via insertions in FRR1
5-fluorocytosine (5FC) via disruptions in UXS1
This temperature-linked genomic instability suggests that the stress of entering a mammalian host environment is itself a mutagenic trigger, driving rapid evolution in real time.
Why This Matters
Drug Resistance in Real Time
Antifungal drug resistance has historically been explained by slow mutation accumulation. This study shows that Cryptococcus can leapfrog adaptation through TE activity, producing resistant strains within the course of an infection.Virulence and Persistence
In addition to drug resistance, TE-driven mutations may also alter virulence traits, including capsule production, melanization, and thermotolerance — all of which are essential for Cryptococcus survival in the host.Climate Change Connection
The researchers point out that as global temperatures rise, environmental fungi may experience greater TE mobilization, potentially enabling non-pathogenic fungi to breach the temperature barrier and cause disease in mammals.
Key Takeaway
This work highlights transposable elements not as “junk DNA,” but as powerful engines of fungal adaptability. In Cryptococcus, TEs are more than passengers in the genome — they’re drivers of rapid microevolution, drug resistance, and perhaps the emergence of new fungal diseases in a warming world.
As Gusa et al. conclude, “temperature-triggered TE mobilization may be a critical, but underappreciated, mechanism of fungal adaptation to the host” (PNAS, 2020).
References
Gusa, A., Williams, J.D., Cho, J.-E., Averette, A.F., Sun, S., Shouse, E.M., Heitman, J., Alspaugh, J.A., & Jinks-Robertson, S. (2020). Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro. Proceedings of the National Academy of Sciences (PNAS), 117(18), 9973–9980. DOI: 10.1073/pnas.2001451117
