Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway
Abstract Pathogenicity mechanisms of the yeast Candida albicans involve filamentous growth, adhesion, invasion, and toxin production. Interestingly, clinical isolates, and other Candida spp., can cause infection independent of filamentation or toxin production. These strains and species often are ch...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61701-5 |
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| author | Sophia U. J. Hitzler Candela Fernández-Fernández Kerstin Günther Axel Dietschmann Hrant Hovhannisyan Anna Möslinger Sophie Austermeier Beatriz Cristóvão Gianluca Vascelli Teresa Zelante Marina Pekmezović Bernardo Ramírez-Zavala Joachim Morschhäuser Oliver Werz Toni Gabaldón Paul M. Jordan Slavena Vylkova Mark S. Gresnigt |
| author_facet | Sophia U. J. Hitzler Candela Fernández-Fernández Kerstin Günther Axel Dietschmann Hrant Hovhannisyan Anna Möslinger Sophie Austermeier Beatriz Cristóvão Gianluca Vascelli Teresa Zelante Marina Pekmezović Bernardo Ramírez-Zavala Joachim Morschhäuser Oliver Werz Toni Gabaldón Paul M. Jordan Slavena Vylkova Mark S. Gresnigt |
| author_sort | Sophia U. J. Hitzler |
| collection | DOAJ |
| description | Abstract Pathogenicity mechanisms of the yeast Candida albicans involve filamentous growth, adhesion, invasion, and toxin production. Interestingly, clinical isolates, and other Candida spp., can cause infection independent of filamentation or toxin production. These strains and species often are characterized as avirulent ex vivo, yet this does not correlate with their potential to cause infection. We hypothesized that specific host factors, which trigger pathogenicity in vivo, are absent in in vitro infection models and thereby clinical isolates can seem avirulent ex vivo. We investigated how albumin, the most abundant protein in humans, impacts infection and cytotoxic potential of C. albicans in vitro. The presence of albumin induces otherwise non-damaging and non-filamentous clinical isolates to cause host cell cytotoxicity. Moreover, avirulent deletion mutants deficient in filamentation, adhesion, or toxin production are restored in their cytotoxicity by albumin. This involves transcriptional and metabolic reprogramming of C. albicans, increasing biofilm formation and production of the oxylipin 13-hydroxyoctadecadienoic acid, driving host cell cytotoxicity. Collectively, our study uncoveres a pathogenicity mechanism by which C. albicans causes epithelial cytotoxicity independent of its conventional virulence mechanisms. This alternative pathogenicity strategy helps to explain the avirulence of clinical isolates ex vivo, when they are separated from the host environment. |
| format | Article |
| id | doaj-art-3664821fe0804d51b3ab4f042a576ef5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3664821fe0804d51b3ab4f042a576ef52025-08-20T03:46:20ZengNature PortfolioNature Communications2041-17232025-07-0116112010.1038/s41467-025-61701-5Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathwaySophia U. J. Hitzler0Candela Fernández-Fernández1Kerstin Günther2Axel Dietschmann3Hrant Hovhannisyan4Anna Möslinger5Sophie Austermeier6Beatriz Cristóvão7Gianluca Vascelli8Teresa Zelante9Marina Pekmezović10Bernardo Ramírez-Zavala11Joachim Morschhäuser12Oliver Werz13Toni Gabaldón14Paul M. Jordan15Slavena Vylkova16Mark S. Gresnigt17Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller UniversityJunior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Life Sciences Department, Barcelona Supercomputing Center (BSC-CNS)Department of Microbial Pathogenicity Mechanisms, Leibniz-HKIDepartment of Microbial Pathogenicity Mechanisms, Leibniz-HKIJunior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Department of Medicine and Surgery, University of PerugiaDepartment of Medicine and Surgery, University of PerugiaJunior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Institute of Molecular Infection Biology, University of WürzburgInstitute of Molecular Infection Biology, University of WürzburgDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller UniversityLife Sciences Department, Barcelona Supercomputing Center (BSC-CNS)Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller UniversitySeptomics Research Center, Friedrich Schiller University, and Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll InstituteJunior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology—Hans-Knöll-Institute (Leibniz-HKI)Abstract Pathogenicity mechanisms of the yeast Candida albicans involve filamentous growth, adhesion, invasion, and toxin production. Interestingly, clinical isolates, and other Candida spp., can cause infection independent of filamentation or toxin production. These strains and species often are characterized as avirulent ex vivo, yet this does not correlate with their potential to cause infection. We hypothesized that specific host factors, which trigger pathogenicity in vivo, are absent in in vitro infection models and thereby clinical isolates can seem avirulent ex vivo. We investigated how albumin, the most abundant protein in humans, impacts infection and cytotoxic potential of C. albicans in vitro. The presence of albumin induces otherwise non-damaging and non-filamentous clinical isolates to cause host cell cytotoxicity. Moreover, avirulent deletion mutants deficient in filamentation, adhesion, or toxin production are restored in their cytotoxicity by albumin. This involves transcriptional and metabolic reprogramming of C. albicans, increasing biofilm formation and production of the oxylipin 13-hydroxyoctadecadienoic acid, driving host cell cytotoxicity. Collectively, our study uncoveres a pathogenicity mechanism by which C. albicans causes epithelial cytotoxicity independent of its conventional virulence mechanisms. This alternative pathogenicity strategy helps to explain the avirulence of clinical isolates ex vivo, when they are separated from the host environment.https://doi.org/10.1038/s41467-025-61701-5 |
| spellingShingle | Sophia U. J. Hitzler Candela Fernández-Fernández Kerstin Günther Axel Dietschmann Hrant Hovhannisyan Anna Möslinger Sophie Austermeier Beatriz Cristóvão Gianluca Vascelli Teresa Zelante Marina Pekmezović Bernardo Ramírez-Zavala Joachim Morschhäuser Oliver Werz Toni Gabaldón Paul M. Jordan Slavena Vylkova Mark S. Gresnigt Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway Nature Communications |
| title | Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway |
| title_full | Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway |
| title_fullStr | Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway |
| title_full_unstemmed | Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway |
| title_short | Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway |
| title_sort | host albumin redirects candida albicans metabolism to engage an alternative pathogenicity pathway |
| url | https://doi.org/10.1038/s41467-025-61701-5 |
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