Scientists at the University of Exeter have identified a genetic process in Candida auris that could lead to new treatments for this dangerous fungal infection. Candida auris poses a significant threat, especially to critically ill patients in hospitals. It is known for its resistance to all major antifungal drugs and has a mortality rate of 45 percent once infection occurs.
First detected in 2008, Candida auris has since caused outbreaks in more than 40 countries, including the UK. The World Health Organization lists it as a critical priority fungal pathogen due to its global impact and increasing case numbers.
Researchers used an innovative approach involving Arabian killifish larvae to study how genes are activated during infection. This model allowed them to observe the pathogen at human body temperatures and avoid traditional animal models like mice or zebrafish.
The team found that Candida auris can form elongated filaments, possibly as a way to search for nutrients. They also identified genes activated during infection that code for nutrient pumps responsible for scavenging iron from their environment.
NIHR Clinical Lecturer Hugh Gifford from the University of Exeter's MRC Center for Medical Mycology said: "Since it emerged, Candida auris has wreaked havoc where it takes hold in hospital intensive care units. It can be deadly for vulnerable patients, and health trusts have spent millions on the difficult job of eradication. We think our research may have revealed an Achilles heel in this lethal pathogen during active infection, and we urgently need more research to explore whether we can find drugs that target and exploit this weakness."
Dr Gifford added: "While there are a number of research steps to go through yet, our finding could be an exciting prospect for future treatment. We have drugs that target iron scavenging activities. We now need to explore whether they could be repurposed to stop Candida auris from killing humans and closing down hospital intensive care units."
The establishment of the Arabian killifish larvae model was supported by an NC3Rs project grant as an alternative method for studying host-pathogen interactions without using mice or zebrafish. Dr Katie Bates, NC3Rs Head of Research Funding, stated: "This new publication demonstrates the utility of the replacement model to study Candida auris infection and enable unprecedented insights into cellular and molecular events in live infected hosts. This is a brilliant example of how innovative alternative approaches can overcome key limitations of traditional animal studies."
The findings were published in Communications Biology under the title 'Xenosiderophore transporter gene expression and clade-specific filamentation in Candida auris killifish (Aphanius dispar) infection.' The study received support from Wellcome, the Medical Research Council (MRC), and NC3Rs.
