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Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans
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The Gram-positive bacterium Enterococcus faecalis and the fungus Candida albicans are both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using a Caenorhabditis elegans model of polymicrobial infection, we discovered that E. faecalis and C. albicans negatively impact each other's virulence. Much of the negative effect of E. faecalis on C. albicans was due to the inhibition of C. albicans hyphal morphogenesis, a developmental program crucial to C. albicans pathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence in E. faecalis . Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibit C. albicans filamentation in the context of an in vitro biofilm. Finally, a screen of an E. faecalis transposon mutant library identified other genes required for suppression of C. albicans hyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome.
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“This is exemplified by a series of articles in the last few years by the Lorenz and Garsin groups, who initially reported on the interactions between Enterococcus faecalis and C. albicans, whereby the bacterium can inhibit C. albicans morphogenesis, biofilm formation, and overall virulence [59].”
From Antifungal therapy of Candida biofilms: Past, present and future (2023) · cites this paper as [59]
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“C. albicans also interacts with several bacterial species found in the gut, such as Enterococcus and Escherichia species; those found in the vagina, such as Lactobacillus species; and those found in the lungs of patients with cystic fibrosis, such as Pseudomonas aeruginosa (13, 34, 54, 78).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [34]
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Metadata
- Authors
- Cruz, M. R., Graham, C. E., Gagliano, B. C., Lorenz, M. C., & Garsin, D. A.
- Affiliations
- The University of Texas Health Science Center at Houston (US)
- Venue
- Infection and Immunity
- Publisher
- American Society for Microbiology
- Published
- 2013-01
- Volume
- 81
- Issue
- 1
- Pages
- 189-200
- ISSN
- 0019-9567 (ISSN-L)
- 1098-5522
- PMC
- PMC3536143
- OpenAlex
- W2165496886
- Cited by
- 188
- References
- 65
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 26 · 2020: 16 · 2019: 19 · 2018: 16 · 2017: 11 · 2016: 12 · 2015: 14 · 2014: 9 · 2013: 7
- FWCI
- 6.63
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Infection and Immunity (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Texas Health Science Center at Houston
- National Institute of Allergy and Infectious Diseases (R01AI075091, R01AI076406, R56AI093699)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Enterococcus faecalis, Candida albicans, hyphal morphogenesis, fungal virulence, co-infection, interkingdom signaling, Caenorhabditis elegans model, biofilm, transposon mutant screen, opportunistic pathogens, human microbiome
- MeSH terms
- Animals, Bacterial Proteins, Candida albicans, Candidiasis, Morphogenesis, Enterococcus faecalis, Virulence, Gram-Positive Bacterial Infections, Caenorhabditis elegans, Biofilms, Hyphae, Quorum Sensing, Coinfection
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