Fungal cells in a biofilm. The green cells are in hibernation mode and the red have been killed by a fungicide. Photo: DTU Vet.

Fungal cells can survive treatment through hibernation

Friday 26 Feb 16
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by Anette Bill-Jessen, Tore Vind Jensen

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Anders Folkesson
Associate Professor
DTU Bioengineering
+4520 12 06 57

Postdoc Rasmus Bojsen and Associate Professor Anders Folkesson from DTU Vet have carried out the trials in collaboration with Birgitte Regenberg from the Department of Biology, University of Copenhagen, and David Gresham from the Department of Biology at New York University.

 

The article is published in Scientific Reports.

Researchers from DTU Vet have demonstrated why fungal infections are difficult to treat in patients with a weakened immune system, and have thus taken the first steps toward a faster and more effective treatment. And this could spell good news for cancer and HIV patients in particular.

Fungal infections are a major problem for cancer and the HIV patients in particular, as their immune system is hampered by the disease and the medical treatment. Such infections are difficult to treat, and today there are only a few effective treatment agents in the market. The problem with fungal infections in patients with weakened immune systems increases as we are becoming better at treating cancer and HIV and prolonging patients’ lives.

New research shows that fungal cells—such as the yeast cell Candida albicans—are capable of going into a kind of hibernation, which makes them invisible to most treatment agents, which attack active cells, explains postdoc Rasmus Bojsen from DTU Vet:

“It is the same mechanism which we witness in nature when yeast cells run out of nutrients. They stop dividing and instead enter hibernation mode to survive the stressful environment. In this way, they can survive for a long time. However, the problem for us is that the same condition makes them resistant to antimicrobial agents,” he says.

Around 1 per cent of fungal cells will in this way survive attacks from antimicrobial agents, and can subsequently wake up and spread when treatment is discontinued. The experiments have even demonstrated that the agent rapamycin, which, among other things, is used in connection with cancer treatment and organ transplantation, amplifies the hibernation mode.

New perception of fungal infections
The general perception among researchers today is that fungal infections are difficult to treat, because fungal cells clump together in a biofilm surrounded by a so-called matrix consisting, among other things, of proteins, sugar, and DNA, and which protects them against fungicides. It is very difficult to say with certainty whether a patient is infected with cells forming biofilm or cells that live singly (planktonic cells). And that knowledge is of great importance to how difficult it is to treat infections.

But now that the researchers behind the study have demonstrated molecular mechanisms that are common for biofilm and planktonic cells, it may be easier to find a treatment that works.

“Treatment of fungal infections will become faster and more effective if we in future focus on common features in biofilm and planktonic cells, especially when considering how difficult it is to diagnose a biofilm in a patient. We should therefore examine the common resistance mechanisms in more detail,” says Rasmus Bojsen who, however, will not rule out the possibility that there may be other mechanisms, which only occur in biofilm.

The researchers at DTU Vet have taken the first step toward a faster and more effective treatment by describing the molecular survival mechanism. The next step will be to develop substances that can make the cells withdraw from their hibernation, so that they again become visible to the treatment agents. This can be done, for example, by using a therapy combining two or more substances. One of the substances will withdraw the cells from their hibernation, the other will kill them.