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Candida auris is the first fungus to spread in hospitals and is resistant to all three major classes of antifungal drugs. New research has discovered that the elimination of a single gene stops the fungus from growing — which could lead to an effective drug treatment.
Photo Credit: CDC
(Public Domain)
Scientific Frontline: Extended "At a Glance" Summary: Therapeutic Target for Candida auris
The Core Concept: Researchers have identified the TRK1 gene and its corresponding protein transporter as essential for potassium uptake in the multidrug-resistant fungus Candida auris, presenting a novel therapeutic target to halt its growth and prevent skin colonization.
Key Distinction/Mechanism: While most fungal cellular machinery closely resembles human eukaryotic structures, the TRK1 potassium transporter in C. auris has no structural counterpart in animal cells. This biological divergence allows for the development of targeted antifungal inhibitors that disrupt fungal colonization without inducing toxicity in human tissues.
Major Frameworks/Components:
- Candida auris Skin Colonization: The pathogenic process of the yeast establishing itself on human epithelial surfaces prior to internal infection.
- Potassium Transport Pathways: The biological dependency of the fungus on external potassium for sustained cellular growth, mediated by the Trk1 protein.
- Gene Deletion Mutagenesis: The experimental methodology used to isolate TRK1 function, demonstrating that the elimination of this single gene stops fungal proliferation.
- Eukaryotic Structural Divergence: The comparative biological framework highlighting the unique structure of the fungal TRK1 transporter versus animal cells, providing a safe pharmacological target.
Branch of Science: Medical Mycology, Microbiology, Biochemistry, Pharmacology.
Future Application: The synthesis of target-specific antifungal therapies, particularly topical inhibitors, designed to block the Trk1 protein and effectively eradicate C. auris from patient skin before it can enter the body via surgical sites or medical devices.
Why It Matters: Candida auris is responsible for severe hospital-acquired infections, with mortality rates reaching 30% to 60% if the fungus enters the bloodstream and induces sepsis. Because emerging strains demonstrate resistance to all three major classes of existing antifungal drugs, identifying a unique, exploitable vulnerability is an urgent necessity for patient survival.
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| Jeniel Nett, MD, PhD Infectious Disease Associate Professor Photo Credit: Courtesy of University of Wisconsin–Madison |
The discovery could prevent infections caused by Candida auris, a drug-resistant fungus and global public health threat that spreads in hospitals and other care settings. A multidisciplinary team of researchers at the University of Wisconsin–Madison has identified a promising new therapeutic candidate against Candida auris, an emerging fungal pathogen that has alarmed health officials worldwide because of its ability to resist multiple antifungal drugs and spread rapidly through hospitals and care facilities.
“It’s a global public health threat,” says Jeniel Nett, a professor in the Department of Medicine at the UW School of Medicine and Public Health. “Candida auris is the first fungus to spread in hospitals and cause serious disease.”
With funding from the National Institutes of Health, Nett led a team that closely studied the yeast in search of any weaknesses that could be exploited in the fight against it. The need is urgent; there are three major classes of antifungal drugs, and certain strains of Candida auris are resistant to all three of them.
While the fungus’s presence on the skin isn’t itself life-threatening, there are many opportunities for internal exposure—whether through surgery, a catheter, or other medical devices—where it can pose a grave danger. Between 30 and 60 percent of patients who develop a Candida auris infection die, usually due to sepsis after the fungus enters the bloodstream.
Most Candida auris infections respond to an available intravenous medication, but even that is showing signs of vulnerability.
“There have been reports of Candida strains developing resistance to that, leading to a very serious infection,” says Nett.
Studying both synthetic conditions and human skin, Nett and her colleagues sought to learn everything they could about what Candida auris needs to colonize skin. The idea is that finding a way to short-circuit the skin colonization process could prevent possible infections.
The team identified potassium as essential to the growth of the fungus. Further, they constructed various mutant versions of Candida auris with specific genes deleted and discovered that the elimination of a single gene was enough to stop the fungus from growing. The gene, called TRK1, controls a protein by the same name that transports the potassium required for Candida auris to grow and colonize skin and other surfaces.
“We’re really excited about this,” says Nett. “We’re very interested in the transporter because it’s structurally different between cells found in animals and in Candida auris, and so we think we could potentially identify drugs that could target it and disrupt the colonization of skin.”
Because fungi and animals are eukaryotes, much of their critical cellular machinery is similar in structure. The fact that TRK1 in Candida auris has no counterpart in animals means that potential drug candidates targeting the fungus may be safe in humans, Nett says.
The team, which also includes researchers in the Department of Biochemistry and the Department of Civil and Environmental Engineering, is now investigating whether its findings extend to other fungal species.
“And we’re starting to look at ways to identify inhibitors of the Trk1 protein,” says Nett. “A treatment of skin colonization would be a great place to start because there currently isn’t anything effective to remove Candida auris from skin.”
Funding: This research received funding from the National Institutes of Health.
Published in journal: Proceedings of the National Academy of Sciences
Title: Trk1 potassium transport is crucial for effective Candidozyma auris skin colonization
Authors: Adam J. Glawe, Emily F. Eix, Chad J. Johnson, Robert Zarnowski, Maisy K. Andes, James Lazarcik, Katherine A. Henzler-Wildman, and Jeniel E. Nett
Source/Credit: University of Wisconsin–Madison | Will Cushman
Edited by: Scientific Frontline
Reference Number: mcb061726_01