05-Aug-2022 - Ruhr-Universität Bochum

This is how highly resistant strains of fungi emerge

Antibiotic resistance is a matter of common knowledge. And the same phenomenon also occurs with drugs against pathogenic fungi. What causes it is still not very well understood.

An international research team has deciphered the mechanism by which the fungus Cryptococcus neoformans is resistant to fungus-specific drugs. It is a yeast-like fungus that can infect humans. Specific drugs, named antifungals, are available for treatment, but they don’t always work – a phenomenon similar to antibiotic resistance. A team from Duke University in the USA and Ruhr-Universität Bochum (RUB) has used genetic, bioinformatic and microbiological techniques to decipher the mechanism underlying this resistance.

“The results are highly relevant for combating fungal infections in clinical practice, veterinary medicine and agriculture,” says Professor Ulrich Kück, Senior Professor in General and Molecular Botany at RUB. He cooperated for the project with the Bochum researcher Dr. Tim Dahlmann and the team headed by Professor Dr. Joe Heitman, who is currently based at Duke University in North Carolina and has been a visiting professor at RUB on several occasions.

Number of fungal infections on the rise

“In the western hemisphere, the number of people with a lowered immune defence is increasing, because life expectancies are rising rapidly and treatment with immunosuppressants after organ transplants is becoming more common,” explains Ulrich Kück. “This is associated with an increase in fungal infections.” Cryptococcus neoformans is one of the most significant human pathogenic fungi responsible for so-called cryptococcosis. It triggers acute infections in immunocompromised patients; and the mortality rate may be as high as 70 per cent. This is because fungal strains that are resistant to the drugs often evolve in hospitals, which makes treatment more difficult. So far, it was unclear which cellular and genetic mechanisms lead to this resistance.

So-called transposons, however, were known to play a role in the resistances. Transposons are jumping genes, i.e. DNA segments that can change their position in the genome and thus affect the function of genes. If a transposon jumps into a gene that’s critical for susceptibility to a drug, it’s possible for resistance to emerge. The mobility of the transposons is controlled by regulatory RNAs, so-called small interfering RNA, or siRNA for short.

RNA mechanism causes resistance

In their current study, the researchers discovered gene mutations in resistant isolates that led to siRNA control being switched off. By introducing an intact copy of the gene, it was possible to restore siRNA control; as a result, the researchers were able to prevent the transposons from jumping and shed light on the cause of resistance. Due to their small size, the gene segments that code for siRNAs are not easy to find in the genome. Tim Dahlmann managed to locate them with special bioinformatic analyses. By identifying the resistance mechanisms, it will be possible to use them for the treatment of mycoses in humans in the future.

Facts, background information, dossiers
  • fungal infections
  • antifungal drugs
  • Cryptococcus neoformans
More about RUB
  • News

    An off switch for aggression

    Researchers from the Ruhr-Universität Bochum (RUB) and colleagues from Bonn have found a connection in the brain that is crucial for aggressive behavior in mice. The so-called P/Q-type calcium channel, which responds to the neurotransmitter serotonin, is crucial. It has long been known that ... more

    Alzheimer's early detection up to 17 years in advance

    The dementia disease Alzheimer's disease has a 15 to 20 year symptom-free course before the first clinical symptoms appear. Using an immuno-infrared sensor developed in Bochum, a research team was able to identify signs of Alzheimer's disease in the blood up to 17 years before the first cli ... more

    Artificial intelligence folds RNA molecules

    The spatial structure of RNA molecules is crucial for their function. But predicting it is a challenge. For the function of many biomolecules, their three-dimensional structure is crucial. Researchers are therefore not only interested in the sequence of the individual building blocks of bio ... more