More resistant fungi challenge scientists

A species found in patients’ blood becomes more virulent at 98.6 °F when exposed to antiviral drugs, a phenomenon that may become more common with global warming

Editorial staff

A group of scientists in China found a fungus in the blood samples of two patients that was previously unknown to infect humans. But what was most striking about the fungus (Rhodosporidiobolus fluvialis) was that it was not only resistant to drugs from the three existing classes of antifungals, but also it became more virulent at 98.6 degrees Fahrenheit (°F), the average body temperature of mammals.

The study was published in Nature Microbiology.

Human body temperature is one of the natural barriers against fungal infections, as most strains cannot survive above 95 °F. For this reason, the emergence of thermotolerant fungi is a public health challenge.

The study’s authors are part of a consortium of health centers in China which, since 2009, has been isolating fungi found in the bloodstream of hospitalized patients.

The initiative began with 12 hospitals and now includes more than 100. The species in question was found circulating in the blood of two elderly men from different cities at different times.

In a mouse infection model, the researchers showed that R. fluvialis became more virulent after treatment with two antifungal drugs from two of the three classes most commonly used in the clinic.

However, this was only the case when it was grown at a mammal’s average body temperature of 98.6 °F.

When treated with Amphotericin B, a drug normally used to fight strains resistant to other classes, it was found that the number of mutations generated by the temperature also created resistance to the drug.

To identify the genetic basis of the resistance, the two fungus strains were sequenced, revealing a duplication of the ERG11 gene, which codes for the target protein of drugs such as fluconazole.

This duplication has already been reported in other fungi resistant to the same class of drugs, the azoles.

However, when researchers deleted the extra copy of the gene, the resistance remained unchanged. What’s more, when they expressed the gene in another species that was susceptible to the drugs, it became highly resistant.

The dangers of high temperatures

Invasive pathogenic fungi are a major cause of morbidity and mortality, particularly in individuals with compromised immune systems, resulting in approximately 3.7 million deaths annually, wrote the authors.

They explain that, in addition to fungi known for their ability to cause disease, factors such as global warming are changing the ecological niches of many fungi, leading to interactions with human society and the emergence of a plethora of new pathogens in recent decades.

“Considering the high diversity of fungi, with recent estimates of 2.2 million to 3.8 million species on Earth, it is believed that the danger and importance of new pathogens is seriously underestimated,” the researchers warn.

In a statement published in the same journal, researchers not involved in the study say the observations challenge current drug susceptibility testing protocols, which are designed to predict the rapid emergence of resistance, as well as doctors’ interpretations of the results.

“As global temperatures rise, not only will thermotolerance be selected for by fungi, but the pool of potential human pathogens will also increase,” write Michael J. Bottery and David W. Denning from the University of Manchester’s School of Biology, Medicine and Health in the UK.

“High temperatures can also lead to increased mutation rates, thereby increasing the genomic adaptability of these microorganisms,” they explain.

The good news is that the authors of the study have found an antimicrobial peptide that is active against R. fluvialis, with no evolution of resistance observed even at high temperatures.

The finding suggests that similar peptides could become an alternative treatment in the future.

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