Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103

Trinh Phan-Canh; Cristina Coman; Michaela Lackner; Nina Troppmair; Christoph Müller; Diana Cerbu; Saskia Seiser; Philipp Penninger; Irina Tsymala; Narakorn Khunweeraphong; Tamires Bitencourt; Andrej Knarr; Sabrina Jenull; Hossein Arzani; Lisa Maria Zenz; Giuseppe Ianiri; Weiqiang Chen; Anuradha Chowdhary; Harry L.T. Mobley; Markus Hartl; Doris Moser; Robert Ahrends; Adelheid Elbe-Bürger; Karl Kuchler

doi:10.1038/s41564-025-02189-z

Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103

Trinh Phan-Canh
, Cristina Coman
, Michaela Lackner
, Nina Troppmair
, Christoph Müller
, Diana Cerbu
, Saskia Seiser
, Philipp Penninger
, Irina Tsymala
, Narakorn Khunweeraphong
, Tamires Bitencourt
, Andrej Knarr
, Sabrina Jenull
, Hossein Arzani
, Lisa Maria Zenz
, Giuseppe Ianiri
, Weiqiang Chen
, Anuradha Chowdhary
, Harry L.T. Mobley
, Markus Hartl

Doris Moser, Robert Ahrends, Adelheid Elbe-Bürger (Korresp. Autor*in), Karl Kuchler (Korresp. Autor*in)

Veröffentlichungen: Beitrag in Fachzeitschrift › Artikel › Peer Reviewed

Abstract

The pronounced skin tropism and pan-antifungal resistance of Candida auris pose a serious global health threat. A key question in C. auris biology is how clinical isolates acquire amphotericin B resistance. Here we demonstrate that a carbonic sensing pathway (CSP) contributes to amphotericin B resistance by modulating mitochondrial energy functions in clinical C. auris isolates. Integrated transcriptomics and proteomics identify the carbonic anhydrase Nce103 and its transcription factors Rca1 and Efg1 as important regulatory components of the CSP. The conversion of CO₂ into bicarbonate sustains energy metabolism required for colonization and fitness on human skin and in nutrient-limited microenvironments. We also show that bacterial skin colonizers engage urease to release CO₂ that sustains C. auris fitness and skin colonization. These findings highlight therapeutic options to re-sensitize C. auris to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.

Originalsprache	Englisch
Seiten (von - bis)	461-475
Seitenumfang	15
Fachzeitschrift	Nature Microbiology
Jahrgang	11
Ausgabenummer	2
DOIs	https://doi.org/10.1038/s41564-025-02189-z
Publikationsstatus	Elektronische Veröffentlichung vor Drucklegung - 2025

Fördermittel

We thank A. Petryshyn, S. Volkan and all other lab members for their technical support and experimental advice. Moreover, we thank N. Chauhan (Center for Discovery and Innovation) for providing clinical isolates; T. O’Meara (University of Michigan Medical School) for providing the plasmids pTO135, pTO149 and pTO136; C. Chen (Chinese Academy of Sciences) and S. Znaidi (Memorial University of Newfoundland) for providing plasmid pCB323; M. Bradley (Queen Mary University of London) for the gift of Cy5-conjugated AMB; A. Brakhage (Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute) for providing Trichophyton benhamiae (WT and stuA mutants); C. Freystätter (Medical University of Vienna) for providing the skin samples. We thank C. Nobile (University of California, Merced) and A.E.-B. for serving as members on the PhD Thesis Committee of T.P.-C; P.-L. Luu (Thong Nhat Hospital, Ho Chi Minh City) for guiding in bioinformatics. We are grateful to human volunteers donating native skin tissues. K.K. was supported by grants from the Austrian Science Fund (ChromFunVir - P-32582-B08, Candidomics - P-33425, and in part by FWF-SFB70-08). A.E.-B. received funds from the Austrian Science Fund - FWF (P-31485-B30) and the LEO Foundation (LF-OC-23-001332). T.P.-C. was supported by a Student Fellowship, Ernst Mach Grant, a Bernd Rode Award 2024 from ASEAN – European Academic University Network (ASEA-UNINET) network and the ESCMID Research Grant 2023 from the European Society of Clinical Microbiology and Infectious Diseases; T.P.-C. was also supported in part by the LEO Foundation (LF-OC-23-001332). H.A., I.T. and T.P.-C. were supported by the FWF-funded PhD training program (TissueHome – FWF-DOC32-B28). N.K. was supported in part by the LEO Foundation (LF-OC-23-001332). A.C. is a fellow of the Canadian Institute for Advanced Research, Fungal Kingdom. N.N.T., C.C. and R.A. received support from the Faculty of Chemistry, University of Vienna - Mass Spectrometry Centre, with funding from the Vienna Doctoral School in Chemistry and DigiOmics4Austria: BMBWF ‘(Digitale) Forschungsinfrastrukturen’. Open access funding provided by Medical University of Vienna.

Träger	Trägernummer
Fonds zur Förderung der wissenschaftlichen Forschung (FWF)	FWF-SFB70-08, ChromFunVir - P-32582-B08, Candidomics - P-33425, TissueHome - FWF-DOC32-B28, P-31485-B30
European Society of Clinical Microbiology and Infectious Diseases (ESCMID)	ESCMID Research Grant 2023
Leo Pharma AS	LF-OC-23-001332

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

SDG 3 – Gesundheit und Wohlergehen

ÖFOS 2012

106022 Mikrobiologie
104004 Chemische Biologie
301304 Medizinische Biologie
301902 Immunologie

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10.1038/s41564-025-02189-z

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Zitationsweisen

Phan-Canh, T., Coman, C., Lackner, M., Troppmair, N., Müller, C., Cerbu, D., Seiser, S., Penninger, P., Tsymala, I., Khunweeraphong, N., Bitencourt, T., Knarr, A., Jenull, S., Arzani, H., Zenz, L. M., Ianiri, G., Chen, W., Chowdhary, A., Mobley, H. L. T., ... Kuchler, K. (2025). Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103. Nature Microbiology, 11(2), 461-475. Vorzeitige Online-Publikation. https://doi.org/10.1038/s41564-025-02189-z

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title = "Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103",

abstract = "The pronounced skin tropism and pan-antifungal resistance of Candida auris pose a serious global health threat. A key question in C. auris biology is how clinical isolates acquire amphotericin B resistance. Here we demonstrate that a carbonic sensing pathway (CSP) contributes to amphotericin B resistance by modulating mitochondrial energy functions in clinical C. auris isolates. Integrated transcriptomics and proteomics identify the carbonic anhydrase Nce103 and its transcription factors Rca1 and Efg1 as important regulatory components of the CSP. The conversion of CO2 into bicarbonate sustains energy metabolism required for colonization and fitness on human skin and in nutrient-limited microenvironments. We also show that bacterial skin colonizers engage urease to release CO2 that sustains C. auris fitness and skin colonization. These findings highlight therapeutic options to re-sensitize C. auris to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.",

author = "Trinh Phan-Canh and Cristina Coman and Michaela Lackner and Nina Troppmair and Christoph M{\"u}ller and Diana Cerbu and Saskia Seiser and Philipp Penninger and Irina Tsymala and Narakorn Khunweeraphong and Tamires Bitencourt and Andrej Knarr and Sabrina Jenull and Hossein Arzani and Zenz, \{Lisa Maria\} and Giuseppe Ianiri and Weiqiang Chen and Anuradha Chowdhary and Mobley, \{Harry L.T.\} and Markus Hartl and Doris Moser and Robert Ahrends and Adelheid Elbe-B{\"u}rger and Karl Kuchler",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025. Accession Number WOS:001645239600001 PubMed ID 41436656",

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doi = "10.1038/s41564-025-02189-z",

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Phan-Canh, T, Coman, C, Lackner, M, Troppmair, N, Müller, C, Cerbu, D, Seiser, S, Penninger, P, Tsymala, I, Khunweeraphong, N, Bitencourt, T, Knarr, A, Jenull, S, Arzani, H, Zenz, LM, Ianiri, G, Chen, W, Chowdhary, A, Mobley, HLT, Hartl, M, Moser, D, Ahrends, R, Elbe-Bürger, A & Kuchler, K 2025, 'Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103', Nature Microbiology, Jg. 11, Nr. 2, S. 461-475. https://doi.org/10.1038/s41564-025-02189-z

TY - JOUR

T1 - Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103

AU - Phan-Canh, Trinh

AU - Coman, Cristina

AU - Lackner, Michaela

AU - Troppmair, Nina

AU - Müller, Christoph

AU - Cerbu, Diana

AU - Seiser, Saskia

AU - Penninger, Philipp

AU - Tsymala, Irina

AU - Khunweeraphong, Narakorn

AU - Bitencourt, Tamires

AU - Knarr, Andrej

AU - Jenull, Sabrina

AU - Arzani, Hossein

AU - Zenz, Lisa Maria

AU - Ianiri, Giuseppe

AU - Chen, Weiqiang

AU - Chowdhary, Anuradha

AU - Mobley, Harry L.T.

AU - Hartl, Markus

AU - Moser, Doris

AU - Ahrends, Robert

AU - Elbe-Bürger, Adelheid

AU - Kuchler, Karl

PY - 2025

Y1 - 2025

N2 - The pronounced skin tropism and pan-antifungal resistance of Candida auris pose a serious global health threat. A key question in C. auris biology is how clinical isolates acquire amphotericin B resistance. Here we demonstrate that a carbonic sensing pathway (CSP) contributes to amphotericin B resistance by modulating mitochondrial energy functions in clinical C. auris isolates. Integrated transcriptomics and proteomics identify the carbonic anhydrase Nce103 and its transcription factors Rca1 and Efg1 as important regulatory components of the CSP. The conversion of CO2 into bicarbonate sustains energy metabolism required for colonization and fitness on human skin and in nutrient-limited microenvironments. We also show that bacterial skin colonizers engage urease to release CO2 that sustains C. auris fitness and skin colonization. These findings highlight therapeutic options to re-sensitize C. auris to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.

AB - The pronounced skin tropism and pan-antifungal resistance of Candida auris pose a serious global health threat. A key question in C. auris biology is how clinical isolates acquire amphotericin B resistance. Here we demonstrate that a carbonic sensing pathway (CSP) contributes to amphotericin B resistance by modulating mitochondrial energy functions in clinical C. auris isolates. Integrated transcriptomics and proteomics identify the carbonic anhydrase Nce103 and its transcription factors Rca1 and Efg1 as important regulatory components of the CSP. The conversion of CO2 into bicarbonate sustains energy metabolism required for colonization and fitness on human skin and in nutrient-limited microenvironments. We also show that bacterial skin colonizers engage urease to release CO2 that sustains C. auris fitness and skin colonization. These findings highlight therapeutic options to re-sensitize C. auris to antifungal treatments, as well as to prevent skin colonization by blocking the CSP.

UR - https://www.scopus.com/pages/publications/105025756878

U2 - 10.1038/s41564-025-02189-z

DO - 10.1038/s41564-025-02189-z

M3 - Article

C2 - 41436656

AN - SCOPUS:105025756878

SN - 2058-5276

VL - 11

SP - 461

EP - 475

JO - Nature Microbiology

JF - Nature Microbiology

IS - 2

ER -

Candida auris skin tropism and antifungal resistance are mediated by carbonic anhydrase Nce103

Abstract

Fördermittel

UN SDGs

ÖFOS 2012

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