Like a late-night, post-apocalyptic plot, rising temperatures cause fungi to mutate, not just hyper-susceptible, but drug-resistant. Jingjing Huang, a researcher at Nanjing Medical University, and colleagues warn that this is due to global warming.
New paper said “The threat and importance of emerging fungal pathogens is seriously underappreciated, temperature-dependent mutagenesis may allow the development of pan-drug resistance and hypervirulence in fungi and may support the idea that global warming may promote the evolution of new fungal pathogens.”
Fungal infections kill about 3.75 million people every year, even though they prefer lower temperatures than our bodies. But previous research has shown that adapting fungi to warmer conditions can change their physiology.
Scientists have recently identified the first fungus to emerge as a pathogen due to climate change: Candida auris. As other fungi, such as C. auris, are more resistant to heat, many species will find the body of a sheltered mammal where they can thrive.
By analyzing records of fungal infections from 96 hospitals in China between 2009 and 2019, Huang and his team identified a group of fungi that had never been seen in humans before. Rhodosporidiobolus appeared independently in two unrelated cases.
Strain NJ103 was isolated from a 61-year-old immunocompromised man who died of multiple organ failure despite fluconazole and caspofungin antifungal therapy. Strain TZ579 was isolated from an 85-year-old man who died of respiratory failure after treatment with fluconazole.
The researchers isolated eight strains of Rhodosporidiobolus, including two strains and others, and exposed them to an average human body temperature of 37°C (98.6°F) in the laboratory. Both R. fluvialis and R. nylandii strains were heat tolerant – in R. fluvialis, a hot environment even induced the colonial pseudohypal phase to be more aggressive than single cell yeast.
When injected into mice, both strains thrived.
In its marine form, R. fluvialis not only thrived in hot conditions, but it was more resistant to immune macrophage cells, killing most of them instead of being killed by them. Both R. fluvialis and R. nylandii are resistant to the three most commonly used antifungal drugs – fluconazole, caspofungin, and amphotericin B.
“R. fluvialis is sensitive to 5-fluorocytosine; however, we found that R. fluvialis was able to quickly produce mutants resistant to 5-fluorocytosine,” the researchers said. “The rate of complete resistance in R. fluvialis was remarkable.”
Huang and his colleagues discovered a substance that Rhodosporidiobolus could not easily adapt to: polymyxin B, an FDA-approved bactericide. Unfortunately, this drug is toxic to neurons and kidney cells.
As global temperatures warm, these morphological changes may increase our exposure to dangerous fungi in the future. More forms of fungicide are needed.
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