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Updated: Jun 5, 2025
An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
Published on: July 1, 2020
Candida albicans enhances Staphylococcus aureus virulence by progressive generation of new phenotypes
Betsy Verónica Arévalo-Jaimes1,2, Eduard Torrents1,2
1Bacterial infections and antimicrobial therapies group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac Street 10, 08037, Barcelona, Spain.
Abstract:
Candida albicans and Staphylococcus aureus have been co-isolated from several biofilm-associated diseases, including those related to medical devices. This association confers advantages to both microorganisms, resulting in detrimental effects on the host. To elucidate this phenomenon, the present study investigated colony changes derived from non-physical interactions between C. albicans and S. aureus. We performed proximity assays by confronting colonies of the yeast and the bacteria on agar plates at six different distances for 9-10 days. We found that colony variants of S. aureus originated progressively after prolonged exposure to C. albicans proximity, specifically in response to pH neutralization of the media by the fungi. The new phenotypes of S. aureus were more virulent in a Galleria mellonella larvae model compared to colonies grown without C. albicans influence. This event was associated with an upregulation of RNA III and agrA expression, suggesting a role for α-toxin. Our findings indicate that C. albicans enhances S. aureus virulence by inducing the formation of more aggressive colonies. This highlights the importance of understanding the intricate connection between environmental responses, virulence and, fitness in S. aureus pathogenesis.
Insights
Candida albicans proximity causes Staphylococcus aureus to form more virulent colonies by neutralizing pH. This fungal interaction enhances bacterial virulence, impacting host pathogenesis.
Area of Science:
- Microbiology
- Pathogenesis
- Microbial Interactions
Background:
- Candida albicans and Staphylococcus aureus frequently co-occur in biofilm-associated infections, particularly with medical devices.
- This polymicrobial association benefits both species and harms the host.
- Understanding non-physical interactions is crucial for elucidating synergistic virulence.
Purpose of the Study:
- To investigate colony variations in Staphylococcus aureus resulting from proximity to Candida albicans.
- To determine the impact of fungal-bacterial non-physical interactions on bacterial virulence.
Main Methods:
- Proximity assays were conducted by co-culturing C. albicans and S. aureus colonies on agar plates at varying distances (6 distances) for 9-10 days.
- Phenotypic changes in S. aureus colonies were observed.
- Virulence of S. aureus variants was assessed using a Galleria mellonella larvae model.
- Gene expression analysis (RNA III and agrA) was performed.
Main Results:
- Prolonged proximity to C. albicans induced colony variants in S. aureus, linked to fungal-mediated pH neutralization.
- These S. aureus variants exhibited increased virulence in the Galleria mellonella model compared to controls.
- Upregulation of RNA III and agrA expression was observed, suggesting a role for alpha-toxin.
Conclusions:
- Candida albicans enhances Staphylococcus aureus virulence through non-physical interactions, leading to the emergence of more aggressive bacterial colonies.
- Fungal-induced environmental modifications (e.g., pH changes) can significantly impact bacterial virulence and pathogenesis.
- This study underscores the complex interplay between environmental cues, gene regulation, and virulence in polymicrobial infections.
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