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Published on: June 13, 2021
Trk1 potassium transport is crucial for effective Candidozyma auris skin colonization
Adam J Glawe1, Emily F Eix1,2, Chad J Johnson1
1Department of Medicine, University of Wisconsin-Madison, Madison, WI 53706.
Abstract:
The recently emergent fungal pathogen Candidozyma (Candida) auris has produced numerous outbreaks of invasive disease in hospitals worldwide. It is the first fungal pathogen categorized as a global public health threat due to its ability to readily colonize skin, spread efficiently person-to-person, and cause invasive infection with high mortality. Skin colonization not only promotes healthcare spread but also leads to invasive infection via the insertion of medical devices through skin. However, the mechanisms underlying C. auris survival in the skin niche remain poorly understood. Here, we identify potassium (K+) as a crucial nutrient for efficient growth in this environment. We show that putative high-affinity K+ transporter Trk1 is required for C. auris growth on human skin ex vivo. Disruption of TRK1 significantly impairs K+ uptake and leads to plasma membrane hyperpolarization, a lower intracellular pH, and sensitivity to cationic stress. These findings demonstrate that TRK1 is necessary for maintaining K+ homeostasis during C. auris colonization of human skin, shedding light on pathogenesis for this emerging threat. Given that TRK1 has no known human homologs, the gene product may serve as a promising therapeutic target for development of novel strategies directed at C. auris propagating on skin.
Insights
Potassium (K+) is vital for the growth of the dangerous fungus Candida auris on human skin. Targeting the TRK1 transporter could prevent skin colonization and infection by this global health threat.
Area of Science:
- Mycology
- Infectious Diseases
- Medical Microbiology
Background:
- Candida auris is an emerging global health threat causing hospital outbreaks.
- Its ability to colonize skin facilitates healthcare transmission and invasive infections.
- Mechanisms of C. auris skin survival are poorly understood.
Purpose of the Study:
- To investigate nutrient requirements for C. auris growth on human skin.
- To identify specific molecular targets for controlling C. auris skin colonization.
Main Methods:
- Utilized human skin ex vivo models.
- Disrupted the TRK1 gene in C. auris.
- Assessed K+ uptake, membrane potential, and intracellular pH.
- Evaluated sensitivity to cationic stress.
Main Results:
- Identified potassium (K+) as essential for C. auris skin growth.
- The high-affinity K+ transporter Trk1 is crucial for C. auris skin colonization.
- TRK1 disruption impairs K+ uptake, leading to membrane hyperpolarization and altered intracellular pH.
Conclusions:
- TRK1 is essential for maintaining K+ homeostasis during C. auris skin colonization.
- The TRK1 gene product is a potential therapeutic target to combat C. auris skin propagation.
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