Synergistic interactions between <i>Candida albicans</i> and <i>Enterococcus faecalis</i> promote toxin-dependent host cell damage
The fungus <i>Candida albicans</i> and the Gram-positive bacterium <i>Enterococcus faecalis</i> share mucosal niches in the human body. As opportunistic pathogens, both are found to expand population size during dysbiosis, and can cause severe systemic infections in susceptible individuals. Here, we show that the presence of <i>C. albicans</i> results in increased host cell damage by <i>E. faecalis</i>. Furthermore, <i>E. faecalis</i> aggravates oropharyngeal candidiasis in mice. Increased damage is mediated by enterococcal cytolysin, and involves both physical interaction and altered glucose availability. Physical interaction promotes accumulation of bacteria on host cells, facilitating contact of cytolysin with host cells. Glucose depletion by the metabolic activity of the fungus sensitized host cells to cytolysin. This work illustrates how a complex interplay between fungi and bacteria can result in detrimental consequences for the host.
Authors
- Bettina Löffler (ORCID: https://orcid.org/0009-0009-6792-9328)
- Ketema Abdissa
- Anna Czapka (ORCID: https://orcid.org/0000-0002-6849-7020)
- Sándor Nietzsche (ORCID: https://orcid.org/0000-0002-1198-6464)
- P. Brandt (ORCID: https://orcid.org/0009-0002-4345-3432)
- Slavena Vylkova
- Maria J. Niemiec (ORCID: https://orcid.org/0000-0001-5667-6032)
- Nicolas Millet (ORCID: https://orcid.org/0000-0002-4644-7153)
- Alexander S. Mosig (ORCID: https://orcid.org/0000-0002-5687-2444)
- Ilse D. Jacobsen (ORCID: https://orcid.org/0000-0002-6033-9984)
- Mark Veleba (ORCID: https://orcid.org/0000-0002-9516-8660)
- Franziska Hoffmann (ORCID: https://orcid.org/0000-0002-6872-924X)
- Mike Marquet (ORCID: https://orcid.org/0000-0003-4344-8289)
- Mario Kapitan
- Kimberly A. Kline (ORCID: https://orcid.org/0000-0002-5472-3074)
- Marc Swidergall (ORCID: https://orcid.org/0000-0002-5261-6267)
- Oliwia Makarewicz (ORCID: https://orcid.org/0000-0002-4404-1862)
- Anna Lange
- Md Estiak Khan Chowdhury
Institutions
- University of Geneva (CH)
- Toho University (JP)
- University of California, Los Angeles (US)
- Nanyang Technological University (SG)
- UCLA Medical Center (US)
- Jena University Hospital (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Singapore Centre for Environmental Life Sciences Engineering (SG)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Institute of Infection and Immunity (CA)
- Harbor–UCLA Medical Center (US)
- Friedrich Schiller University Jena (DE)
- University of Tübingen (DE)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1073/pnas.2505310122
- Citations
- 4
- Primary Topic
- Antifungal resistance and susceptibility
- Type
- article
- Field-Weighted Citation Impact
- 5.58