KU Leuven team discovers that resistance to one antifungal medicine increases the efficacy of a different antifungal medicine
Because Candida auris can easily develop resistance and because there is a limited range of antifungal medicine available, doctors are often faced with having exhausted all treatment options. New KU Leuven research shows that resistance to one treatment can increase the efficacy of a different treatment. This way, the feared resistance can be used as a weapon against this dangerous fungal infection. The research results have been published in Nature Microbiology today.
Did you know that with each breath we take, we inhale one to ten fungal spores? That means that we can inhale up to ten billion fungal spores over the course of one day. The good news is that most of these fungus are harmless and even essential for a healthy body. There is, however, one fungus that has received the 'top urgency' label from the World Health Organization (WHO). Candida auris is a new type of fungus that was first discovered in 2009. It can be very dangerous, specifically for people with a weakened immune system, with a morality rate of 30 to 70%. The biggest problem with this kind of Candida auris infection is that the fungus very quickly becomes resistant to the small range of antifungal medicine available.
KU Leuven biologists studied how the fungus developed resistance and they gained insight into how to prevent and get round this resistance.
Preventing and 'treating' resistance
The team treated C. auris in the lab with different types of antifungal medicine and examined, with DNA analysis, which genetic mutations the fungus made to gain resistance to the medicine. 'Surprisingly, we discovered that mutations that generate resistance to one type of medicine can increase sensitivity to other types of medicine,' explains microbiologist Professor Patrick Van Dijck. The scientific name for this process is 'collateral sensitivity', which is a familiar process in antibiotic resistance and in the treatment of tumours.
It is very important to treat patients in an efficient way. Because of the small range of antifungal medicine available, there can be severe consequences when patients with a C. auris infection develop a resistance.
Professor Patrick Van Dijck
'We discovered that we can prevent and even 'treat' resistance once it has spread, by alternating different types of antifungal medicine in a specific way in a treatment,' adds Postdoctoral Researcher Hans Carolus.
Ready to implement but not a one-size-fits-all
The advantage of our study is that we used existing antifungal medicine. Developing new medicine is a very slow and expensive process. We did not develop any new medicine. Instead, we studied how we can optimise the administration schedule to maximally prevent resistance. Doctors can already use our findings.
Postdoctoral Researcher Hans Carolus
'However, we can't generalise. There isn't one universal antifungal treatment that would cover all bases. C. auris can gain resistance in different ways. Depending on the type of mutation, one treatment will generate better results than the other. Because it can take a few days for results from sensitivity tests to come in, doctors can struggle to determine the right treatment. That is why fast sensitivity tests based on mutations can be an interesting tool in the future. They would allow doctors to respond quickly and administer the specific antifungal medicine that best prevents or combats resistance.'
