Candida auris is especially dangerous for people who are already critically ill, leaving hospitals highly exposed to outbreaks. Although the fungus can exist on the skin without causing symptoms, patients who depend on ventilators face a much greater risk. Once infection occurs, about 45 percent of patients die, and the fungus is resistant to all major types of antifungal drugs. This resistance makes treatment extremely challenging and allows the pathogen to persist in hospital wards.

A global health threat with mysterious origins

The infection was first detected in 2008, and its origin is still unknown. Since then, outbreaks have been reported in more than 40 countries, including the UK. Candida auris, also called Candidozyma auris, is now recognized as a serious global health threat and appears on the World Health Organization’s critical priority fungal pathogens list. In the UK, reported cases have continued to rise steadily.

Studying infection in a living model

Researchers at the University of Exeter have now taken a major step forward by examining how genes are activated during Candida auris infection. This marks the first time such genetic activity has been studied in a living host using an approach based on fish larvae. The study was published in the Nature portfolio journal Communications Biology and was supported by Wellcome, the Medical Research Council (MRC), and the National Center for Replacement, Reduction and Refinement (NC3Rs).

The researchers say the results could help identify a biological target for new antifungal treatments or even allow existing drugs to be reused, if the same genetic behavior is confirmed during infection in humans.

The project was co-led by NIHR Clinical Lecturer Hugh Gifford of the University of Exeter’s MRC Center for Medical Mycology (CMM). He 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.”

Why traditional research models fell short

One of the biggest obstacles in studying Candida auris has been its ability to survive high temperatures. When combined with its unusually strong tolerance for salt, this has led some researchers to suggest it may have originated in tropical oceans or marine animals. These traits also made it difficult to study using conventional laboratory models.

To overcome this, the Exeter team developed a new infection model using Arabian killifish. The eggs of this species can survive at temperatures similar to the human body, making them suitable for observing infection in conditions that closely resemble real illness.

Genetic activity reveals possible vulnerabilities

During the experiments, researchers observed that Candida auris can change its shape by forming elongated fungal structures known as filaments. These structures may help the fungus search for nutrients while infecting a host.

The team also analyzed which genes were activated or switched off during infection to identify possible weak points. Several of the genes that became active are responsible for producing nutrient pumps that capture iron-scavenging molecules and transport iron into fungal cells. Because iron is essential for survival, this process may represent a critical vulnerability.

Co-senior author Dr. Rhys Farrer of the University of Exeter’s MRC Centre for Medical Mycology said: “Until now, we’ve had no idea what genes are active during infection of a living host. We now need to find out if this also occurs during human infection. The fact that we found genes are activated to scavenge iron gives clues to where Candida auris may originate, such as an iron-poor environment in the sea. It also gives us a potential target for new and already existing drugs.”

Hope for future treatments

Dr. Gifford, who also works as a resident physician in intensive care and respiratory medicine at the Royal Devon & Exeter Hospital, emphasized the clinical importance of the findings. He said: “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 Arabian killifish larvae model was developed with support from an NC3Rs project grant as an alternative to using mouse and zebrafish models, which are commonly used to study interactions between pathogens and their hosts. Dr. Katie Bates, NC3Rs Head of Research Funding, said: “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 paper is titled ‘Xenosiderophore transporter gene expression and clade-specific filamentation in Candida auris killifish (Aphanius dispar) infection’ and is published in the Nature portfolio journal Communications Biology.

The imaging system is designed to detect extremely weak signals from surface-enhanced Raman scattering (SERS) nanoparticles that are engineered to attach to tumor markers. Once these nanoparticles are applied to a sample or to the area being examined, the system reads their Raman signal and automatically highlights regions that are more likely to contain tumor tissue.

“Traditional methods for cancer-related diagnosis are time-consuming and labor-intensive because they require staining tissue samples and having a pathologist look for any abnormalities,” said research team leader Zhen Qiu from the Institute for Quantitative Health Science and Engineering (IQ), Michigan State University. “While our system would not immediately replace pathology, it could serve as a rapid screening tool to accelerate diagnosis.”

Published results show major gains in sensitivity

In Optica, Optica Publishing Group’s journal for high-impact research, Qiu and colleagues report that their system can distinguish cancerous cells from healthy ones while detecting Raman signals that are about four times weaker than those measured by a comparable commercial system. This improved sensitivity comes from combining a swept-source laser — which changes wavelength during analysis — with an ultra-sensitive detector called a superconducting nanowire single-photon detector (SNSPD).

“This technology could eventually enable portable or intraoperative devices that enable clinicians to detect cancers at earlier stages, improve the accuracy of biopsy sampling and monitor disease progression through less invasive testing,” said Qiu. “Ultimately, such advances could enhance patient outcomes and reduce diagnostic delays, accelerating the path from detection to treatment.”

Pushing detection limits with superconducting detectors

Qiu’s lab studies how SNSPDs can be used to enhance a range of imaging technologies. SNSPDs rely on a superconducting wire that can detect individual particles of light, allowing the system to capture extremely weak optical signals at high speed while keeping background noise very low.

For this project, the researchers aimed to build a platform that could measure Raman signals far fainter than those detected by existing Raman systems. Raman imaging works by mapping a sample’s chemical composition through the unique light-scattering fingerprints of its molecules. These signals can be strengthened by using SERS nanoparticles.

“Combining this advanced detector with a swept-source Raman architecture that replaces a bulky camera and collects light more efficiently resulted in a system with a detection limit well beyond that of comparable commercial systems,” said Qiu. “Also, the fiber coupling configuration and compact design facilitate system miniaturization and future clinical translation.”

Strong tumor contrast across multiple sample types

To test the system, the team used SERS nanoparticles coated with hyaluronan acid, which enables the particles to bind to CD44, a surface protein found on many tumor cells. Initial experiments with simple nanoparticle solutions showed that the system could reach femtomolar sensitivity. The researchers then applied the imaging platform to cultured breast cancer cells, mouse tumors, and healthy tissue samples.

“The SERS signals were strongly concentrated in tumor samples, with only minimal background detected in healthy tissue,” said Qiu. “This demonstrates both the system’s exceptional sensitivity and its ability to provide reliable tumor-versus-healthy contrast. Moreover, by adjusting or substituting the targeting molecule, this method could be adapted for other cancer types.”

Next steps toward clinical use

According to the researchers, additional work is needed before the system can be used in clinical settings. Future improvements will focus on increasing readout speed and expanding validation studies. The team is exploring faster laser sources, including VCSELs, and testing whether narrowing the sweep range can further improve performance. They also plan multiplexing experiments that use different nanoparticles to target multiple biomarkers at the same time.

The researchers acknowledge industry collaborator Quantum Opus, which provided the SNSPD devices used in this work.