Warmer climate may drive fungi to be more dangerous to our health
Pathogen's mutations ramp up as heat rises, causing concern for new infectivity

Date:
January 31, 2023
Source:
Duke University
Summary:
A new study finds that raised temperatures cause a pathogenic fungus
known as Cryptococcus deneoformans to turn its adaptive responses
into overdrive. Heat increases its number of genetic changes,
some of which might presumably lead to higher heat resistance,
and others perhaps toward greater disease-causing potential.


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FULL STORY ==========================================================================
The world is filled with tiny creatures that find us delicious. Bacteria
and viruses are the obvious bad guys, drivers of deadly global pandemics
and annoying infections. But the pathogens we haven't had to reckon with
as much - - yet -- are the fungi.


========================================================================== Pathogenic fungi (Candida, Aspergillus, Cryptococcus and others) are
notorious killers of immune-compromised people. But for the most part,
healthy people have not had to worry about them, and the vast majority
of the planet's potentially pathogenic fungi don't do well in the heat
of our bodies.

But all that may be about to change.

A new study out of Duke University School of Medicine finds that raised temperatures cause a pathogenic fungus known as Cryptococcus deneoformans
to turn its adaptative responses into overdrive. This increases its number
of genetic changes, some of which might presumably lead to higher heat resistance, and others perhaps toward greater disease-causing potential.

Specifically, higher heat makes more of the fungus' transposable elements,
or jumping genes, get up and move around within the fungal DNA, leading
to changes in the way its genes are used and regulated. The findings
appeared Jan. 20 in the Proceedings of the National Academy of Sciences.

"These mobile elements are likely to contribute to adaptation in the environment and during an infection," said postdoctoral researcher Asiya
Gusa Ph.D. of Molecular Genetics and Microbiology in the Duke School
of Medicine.

"This could happen even faster because heat stress speeds up the number
of mutations occurring." This may ring a bell with viewers of the new
HBO series "The Last of Us," where a dystopian hellscape is precipitated
by a heat-adapted fungus that takes over humans and turns them into
zombies. "That's exactly the sort of thing I'm talking about -- minus
the zombie part!" said Gusa who just watched the first episode and who
will join the Duke faculty as an assistant professor later this year.

"These are not infectious diseases in the communicable sense; we don't
transmit fungi to each other," Gusa said. "But the spores are in the
air. We breathe in spores of fungi all the time and our immune systems
are equipped to fight them." Fungal spores are generally larger than
viruses, so your existing stock of face masks against Covid would probably
be sufficient to stop them. That, and your body heat, for now.

"Fungal diseases are on the rise, largely because of an increase in the
number of people who have weakened immune systems or underlying health conditions," Gusa said. But at the same time, pathogenic fungi may be
adapting to warmer temperatures as well.

Working in the lab of Professor Sue Jinks-Robertson, Gusa led research
that focused on three transposable elements that were particularly active
under heat stress in C. deneoformans. But there are easily another 25 or
more transposable elements in that species that could mobilize, she said.

The team used 'long-read' DNA sequencing to see changes that might
otherwise have been missed, Gusa said. Computational analysis allowed
them to map transposons and then see how they had moved. "We have
improved tools now to see these movements that were previously hiding
in our blind spots." Heat stress sped the mutations up. Following 800 generations of growth in laboratory medium, the rate of transposon
mutations was five-times higher in fungi raised at body temperature
(37 Celsius) compared with fungi raised at 30C.

One of the transposable elements, called T1, had a tendency to insert
itself between coding genes, which could lead to changes in the way
genes are controlled. An element called Tcn12 often landed within the
sequence of a gene, potentially disrupting that gene's function and
possibly leading to drug resistance. And a third kind, Cnl1, tended
to land near or in the telomere sequences at the ends of chromosomes,
an effect which Gusa said isn't fully understood.

The mobilization of transposable elements also appeared to increase
more in fungi living in mice than in lab culture. "We saw evidence of
all three transposable elements mobilizing in the fungus genome within
just ten days of infecting the mouse," Gusa said. The researchers suspect
that the added challenges of surviving in an animal with immune responses
and other stressors may drive the transposons to be even more active.

"This is a fascinating study, which shows how increasing global
temperature may affect the fungal evolution in unpredictable directions,"
said Arturo Casadevall MD, PhD, the chair of molecular microbiology & immunology at Johns Hopkins University. "As the world warms, transposons
in soil fungi like Cryptococcus neoformans could become more mobile
and increase genomic changes in ways that could enhance virulence and
drug resistance. One more thing to worry about with global warming!"
Gusa's work was helped by collaboration with Duke labs that also study
fungi, the Joseph Heitman lab in the school of medicine and the Paul
Magwene lab in Trinity Arts & Sciences.

The next phase of this research will be looking at pathogens from human patients who have had a relapsing fungal infection. "We know that these infections can persist and then come back with potential genetic changes."
It's time to get serious about pathogenic fungi, Gusa said. "These kinds
of stress-stimulated changes may contribute to the evolution of pathogenic traits in fungi both in the environment and during infection. They may
be evolving faster than we expected." This research 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)
* RELATED_TOPICS
o Health_&_Medicine
# Immune_System # Genes # Medical_Topics #
Diseases_and_Conditions
o Plants_&_Animals
# Fungus # Microbes_and_More # Microbiology # Organic
* RELATED_TERMS
o Hyperthermia o Personalized_medicine o Heat_shock_protein
o Asbestos o Pandemic o Lead o Microorganism o
Global_spread_of_H5N1

========================================================================== Story Source: Materials provided by Duke_University. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Asiya Gusa, Vikas Yadav, Cullen Roth, Jonathan D. Williams, Eva Mei
Shouse, Paul Magwene, Joseph Heitman, Sue
Jinks-Robertson. Genome-wide analysis of heat stress-stimulated
transposon mobility in the human fungal pathogen Cryptococcus
deneoformans. Proceedings of the National Academy of Sciences,
2023; 120 (4) DOI: 10.1073/pnas.2209831120 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/01/230131160543.htm

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