Genetic Testing Could Improve Treatment for Virulent Multidrug-Resistant Fungus Candida Auris

Candida auris (C. auris), a multidrug-resistant yeast responsible for severe, life-threatening infections, was first identified in 2009. Since its discovery, it has spread globally, causing significant illness in healthcare settings. With a mortality rate estimated between 30% and 60%, C. auris is not only deadly but also difficult to treat. One of the challenges in managing C. auris infections is the existence of various strains, each with distinct genetic characteristics that confer resistance to different antifungal medications. To identify which drugs are effective against a specific strain, clinical laboratories perform susceptibility testing. This process involves growing a sample of the patient’s C. auris alongside different antifungal drugs to observe which one effectively kills the fungus. However, interpreting these test results can be challenging, as minimum inhibitory concentration (MIC) breakpoints—the lowest concentrations of antifungal drugs that stop C. auris growth—have not been fully defined. Consequently, healthcare providers often face delays in selecting the appropriate antifungal treatment, and such delays can be critical, potentially affecting patient outcomes.

Now, a new study published in ADLM's Clinical Chemistry journal, suggests that genetic testing could provide a faster, more accurate way to identify which antifungal drugs will be effective against C. auris infections. The researchers believe that genetic testing could help doctors initiate the right treatment sooner, improving patient outcomes. To explore this possibility, researchers from Columbia University Irving Medical Center (New York City, NY, USA) examined antifungal resistance genes in C. auris samples from 66 patients. These samples were subjected to two types of genetic analysis: whole-genome sequencing (WGS) and Sanger sequencing. These techniques helped identify each strain’s genetic profile. In addition, the samples underwent traditional susceptibility testing, where they were exposed to seven major antifungal drugs.

By comparing the genetic data with the susceptibility test results, the researchers identified several mutations in the FKS1 gene of C. auris that are responsible for resistance to echinocandins, the primary class of antifungal drugs used to treat invasive C. auris infections. Specifically, they discovered that the Ser639Tyr and Arg135Ser mutations in the FKS1 gene are linked to resistance to micafungin and anidulafungin, while the Met690Ile mutation confers resistance to caspofungin. These findings demonstrate that genomic sequencing can pinpoint which drugs a particular strain of C. auris is resistant to, potentially offering an alternative to traditional susceptibility testing.

“With potential resistance to all three major antifungal classes of drugs, C. auris is an emerging public health threat. Early detection of echinocandin resistance by molecular methods could impact treatment course to include novel antifungal agents,” said Dr. Marie C. Smithgall who led the research team. “Overall WGS serves as a powerful tool for molecular surveillance to help monitor, detect, and curb the spread of C. auris.”

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