Related Experiment Video
Updated: Sep 16, 2025
An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
Published on: July 1, 2020
Host albumin redirects Candida albicans metabolism to engage an alternative pathogenicity pathway
Sophia U J Hitzler1, Candela Fernández-Fernández1, Kerstin Günther2
1Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute (Leibniz-HKI), Jena, Germany.
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.
Insights
Human albumin triggers otherwise avirulent Candida albicans to become cytotoxic. This reveals a new mechanism for fungal infections, explaining why some clinical isolates appear harmless outside the body.
Area of Science:
- Microbiology
- Molecular Biology
- Infectious Diseases
Background:
- Candida albicans exhibits several pathogenicity mechanisms, including filamentation, adhesion, invasion, and toxin production.
- Clinical isolates and other Candida species can cause infection independently of these conventional virulence factors.
- The avirulence of some clinical isolates ex vivo does not correlate with their in vivo infection potential, suggesting missing host factors in in vitro models.
Purpose of the Study:
- To investigate the impact of human albumin on the pathogenicity and cytotoxic potential of Candida albicans in vitro.
- To determine if albumin can restore virulence in avirulent Candida albicans strains.
- To elucidate the molecular mechanisms underlying albumin-induced cytotoxicity.
Main Methods:
- In vitro infection models using human epithelial cells and Candida albicans clinical isolates and deletion mutants.
- Assessment of host cell cytotoxicity in the presence and absence of human albumin.
- Transcriptional and metabolic analysis of Candida albicans.
- Quantification of biofilm formation and oxylipin production.
Main Results:
- Human albumin induced cytotoxicity in otherwise non-damaging and non-filamentous Candida albicans clinical isolates.
- Albumin restored cytotoxicity in avirulent deletion mutants lacking filamentation, adhesion, or toxin production.
- Albumin triggered transcriptional and metabolic reprogramming in Candida albicans, leading to increased biofilm formation and production of 13-hydroxyoctadecadienoic acid.
- These changes driven by albumin resulted in significant host cell cytotoxicity.
Conclusions:
- Human albumin activates an alternative pathogenicity mechanism in Candida albicans, leading to epithelial cell cytotoxicity.
- This albumin-dependent mechanism operates independently of conventional virulence factors like filamentation, adhesion, and toxin production.
- The findings explain the apparent avirulence of certain clinical Candida isolates ex vivo and highlight the importance of host factors in fungal pathogenesis.
More Related Videos
08:48Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
09:24Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host
Published on: October 12, 2022
