Climate change and the potential for increased fungal infectivity

 This media comes from the Centers for Disease Control and Prevention's Public Health Image Library (PHIL), with identification number #3771

Warmer climate may drive fungi to be more dangerous to our health. This is based on those fungi classed as pathogenic undergoing mutations that lead to more serious infections as heat rises. This association between temperature increases and pathogenicity causes a concern for new infectivity.

 

New research into fungal infectivity and temperature

The research comes from Duke University and it finds that raised temperatures cause the pathogenic fungus 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.

 

Experiments have shown how higher heat makes more of the fungus' transposable elements more motile within the fungal DNA. This leads to changes in the way its genes are used and regulated.

 

These mobile elements are likely to contribute to adaptation in the environment and during an infection. This also appears to occur more quickly since heat stress speeds up the number of mutations occurring. This is a factor that has consequences in the context of climate change.

 

Fungal diseases are also on the rise as a consequence of more people who have weakened immune systems or underlying health conditions.

 

Three transposable elements

 

The researchers focused on three transposable elements that were particularly active under heat stress in C. deneoformans. However, there are easily another 25 or more transposable elements in that species that could mobilize.

 

The researchers used 'long-read' DNA sequencing to see changes that might otherwise have been missed. Computational analysis enabled them to map transposons and then see how they had moved.

 

It was found that 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 30^oC.

 

One of the transposable elements, called T1, displayed 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.

Laboratory experiments

The mobilization of transposable elements further appears to increase more in fungi living in mice than in laboratory culture. Evidence of all three transposable elements mobilizing in the fungus genome occurred within just ten days of infecting a mouse.

 

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.

Consequence of global warming

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. 

 

 

The next phase of this research will be looking at pathogens from human patients who have had a relapsing fungal infection.

 

The research paper reference is:

 

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

 

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)