Native human and mouse skin infection models to study Candida auris-host interactions
Saskia Seiser1, Hossein Arzani2, Tanya Ayub1
1Medical University of Vienna, Department of Dermatology, Währinger Gürtel 18-20, 1090 Vienna, Austria.
Abstract:
The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need and present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology and immunofluorescence analysis of ex vivo skin biopsies of human adult and fetal, as well as mouse origin infected with C. auris via distinct routes. We demonstrate that an intact skin barrier efficiently protects from C. auris penetration and invasion. Although C. auris readily grows on native human skin, it can reach deeper layers only upon physical disruption of the barrier by needling or through otherwise damaged skin. By contrast, a barrier disruption is not necessary for C. auris penetration of native mouse skin. Importantly, we show that C. auris undergoes morphogenetic changes upon skin penetration, as it acquires pseudohyphal growth phenotypes in deeper human and mouse dermis. Taken together, this new human and mouse skin model toolset yields new insights into C. auris colonization, adhesion, growth and invasion properties of native versus damaged human skin. The results form a crucial basis for future studies on skin immune defense to colonizing pathogens, and offer new options for testing the action and efficacy of topical antimicrobial compound formulations.
Insights
Candida auris (C. auris) invasion of skin requires barrier damage, unlike in mice. New models reveal C. auris morphs into pseudohyphae in deeper skin layers, aiding infection studies.
Area of Science:
- Mycology
- Infectious Diseases
- Dermatology
Background:
- Candida auris (C. auris) is a multidrug-resistant fungal pathogen causing life-threatening infections.
- The World Health Organization identified C. auris as a critical global health threat.
- Understanding C. auris skin interactions is vital for developing effective treatments.
Purpose of the Study:
- To develop novel ex vivo skin models for studying C. auris-host interactions.
- To investigate the role of the skin barrier in C. auris penetration and invasion.
- To analyze C. auris morphogenetic changes upon skin colonization.
Main Methods:
- Utilized histology and immunofluorescence analysis of ex vivo human and mouse skin explants.
- Infected skin biopsies with C. auris via distinct routes, including needling to disrupt the barrier.
- Examined fungal growth, morphology, and tissue penetration.
Main Results:
- An intact skin barrier effectively prevents C. auris penetration and invasion.
- C. auris readily colonizes intact human skin but invades deeper layers only when the barrier is compromised.
- Barrier disruption is not required for C. auris penetration in mouse skin.
- C. auris exhibits pseudohyphal growth in deeper dermal layers of both human and mouse skin.
Conclusions:
- Developed and validated new ex vivo human and mouse skin models for C. auris research.
- Demonstrated the critical role of skin barrier integrity in preventing C. auris infection.
- Identified C. auris morphogenetic adaptation in response to skin penetration.
- Results provide a foundation for studying skin immunity and testing topical antimicrobial agents.
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