A warming climate could make fungi more dangerous to our health

Specifically, higher heat causes many of the fungal transposable elements, or jumping genes, to move around in the fungal DNA, resulting in changes in the way that genes are used and regulated. The findings were published on his January 20th in the Proceedings of the National Academy of Sciences.

“These mobile elements may contribute to adaptation to the environment and during infection,” said postdoctoral researcher Dr. Asiya Gusa. PhD in Molecular Genetics and Microbiology from Duke Medical School. “This could happen even sooner because heat stress accelerates the number of mutations that occur.”

This may sound alarm bells for viewers of HBO’s new series The Last of Us. It depicts a dystopian hellscape where heat-adapted fungi take over humans and turn them into zombies. “That’s exactly what I’m talking about – except for the zombie part!” said Gusa, who just watched the first episode and will join the faculty at Duke University as an assistant professor later this year.

“These are not infections in the contagious sense. We don’t pass the fungus on to each other,” Gusa said. “But spores are in the air. We’re inhaling fungal spores all the time, and our immune system is ready to fight them.

Fungal spores are generally larger than viruses, so the existing stock of face masks against Covid is probably enough to deter them. And your body heat, for now.

“Fungal diseases are on the rise, mainly because more people have weakened immune systems or have underlying medical conditions,” Gusa said. At the same time, however, pathogens may also be adapted to warmer temperatures.

Working in Professor Sue Jinks-Robertson’s lab, Gusa led a study that focused on three transposable elements that were specifically activated under heat stress in C. deneoformans. But there are easily another 25 or more transposable elements in that species that can be recruited, she said.

The team used “long-read” DNA sequencing to identify changes that might otherwise have been missed, Gusa said. Computer analysis allowed us to map the transposons and see how they migrated. “We have improved our tools so that we can see these movements that were previously hidden in our blind spots.”

Heat stress accelerated mutations. After 800 generations of growth on media, the rate of transposon mutations was five times higher in fungi grown at body temperature (37 degrees Celsius) compared to fungi grown at 30 degrees Celsius.

One of the transposable elements, called T1, tends to insert between coding genes and can change the way genes are regulated. Elements called Tcn12 are often within the sequences of genes and can disrupt the function of that gene, potentially leading to drug resistance. And a third species, Cnl1, tended to land near or at telomere sequences at the ends of chromosomes, an effect Gusa says isn’t fully understood.

Recruitment of transposable elements also appeared to be more increased in fungi living in mice than in laboratory cultures. We have seen evidence of mobilization,” Gusa said. The researchers believe that the additional challenges of surviving in animals with immune responses and other stressors may further activate transposons.

Arturo Casadevall MD, PhD, Professor of Molecular Microbiology and Immunology at Johns Hopkins University, said: “As the world warms, transposons in soil fungi like Cryptococcus neoformans may become more mobile, increasing genomic alterations in ways that increase virulence and drug resistance.” One more thing to worry about!”

Gusa’s research was aided by collaborations with the Duke Institute, which also studies fungi, the Joseph Heitman Institute at the School of Medicine, and the Paul Magwen Institute at Trinity Arts and Sciences.

The next phase of this study will examine pathogens from patients with recurrent fungal infections. “We know that these infections can persist and recur with underlying genetic alterations.”

Gusa said it’s time to get serious about pathogenic fungi. “This type of stress stimulus-induced change may contribute to the evolution of fungal virulence traits both in the environment and during infection. They may be evolving faster than we expected.” .”

This work was supported by the National Institutes of Health (R35-GM118077, R21-AI133644, 5T32AI052080, 2T32AI052080, 1K99-AI166094-01, R01-AI039115-24, R01-AI050113-17, R01-AI133654-05) .

Citation: “Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans”, Ashiya Gusa, Vikas Yadav, Karen Ross, Jonathan Williams, Evan Meil ​​Schous, Paul Magwen , Joseph Heitman, Sue Jinx Robertson. Proceedings of the National Academy of Sciences, January 20, 2023. DOI: 10.1073/pnas.2209831120

Online – https://www.pnas.org/doi/10.1073/pnas.2209831120