Study finds how highly resistant strains of fungal infections emerge

Antibiotic resistance is a well-known issue. The similar thing happens when medications are used to treat pathogenic fungus. What causes it is still poorly known.

“The results are highly relevant for combating fungal infections in clinical practice, veterinary medicine and agriculture,” says Professor Ulrich Kuck, Senior Professor in General and Molecular Botany at RUB. He cooperated on 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 Kuck. “This is associated with an increase in fungal infections.”

Cryptococcus neoformans is one of the most important human pathogenic fungus, causing cryptococcosis. It causes acute infections in immunocompromised persons, and the fatality rate can reach 70%. This is because drug-resistant fungus species frequently emerge in hospitals, making treatment more challenging. It was previously unknown which cellular and genetic pathways cause this resistance.

However, transposons were recognised to have a role in the resistances. Jumping genes are DNA segments that may vary their location in the genome and consequently impact gene activity. If a transposon inserts itself into a gene that is required for drug sensitivity, resistance may develop.

Transposon mobility is regulated by regulatory RNAs, often known as small interfering RNAs, or siRNA for short.

RNA mechanism causes resistance

The researchers detected gene changes in resistant isolates that resulted in siRNA control being turned off in their present investigation. It was feasible to restore siRNA control by inserting an entire copy of the gene; as a consequence, the researchers were able to prevent the transposons from jumping and gave information on the source of resistance. The gene segments that code for siRNAs are difficult to detect in the genome due to their modest size. Tim Dahlmann was able to find them using bioinformatic analysis. By finding resistance mechanisms, it will be feasible to employ them in the future to treat mycoses in humans.