MSGID: 1:317/3 63d9eaf2   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
   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   
      
   --- up 48 weeks, 1 day, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 226/30 227/114 229/110   
   SEEN-BY: 229/111 112 113 114 307 317 400 426 428 470 664 700 292/854   
   SEEN-BY: 298/25 305/3 317/3 320/219 396/45   
   PATH: 317/3 229/426